Browse TGFB1

Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted, extracellular space, extracellular matrix
Domain PF00019 Transforming growth factor beta like domain
PF00688 TGF-beta propeptide
Function

Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts (By similarity). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP) (PubMed:25310401). Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells. Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus (PubMed:25893292). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (PubMed:25893292).

> Gene Ontology
 
Biological Process GO:0000018 regulation of DNA recombination
GO:0000060 protein import into nucleus, translocation
GO:0000075 cell cycle checkpoint
GO:0000271 polysaccharide biosynthetic process
GO:0001501 skeletal system development
GO:0001503 ossification
GO:0001558 regulation of cell growth
GO:0001570 vasculogenesis
GO:0001654 eye development
GO:0001655 urogenital system development
GO:0001657 ureteric bud development
GO:0001658 branching involved in ureteric bud morphogenesis
GO:0001666 response to hypoxia
GO:0001667 ameboidal-type cell migration
GO:0001763 morphogenesis of a branching structure
GO:0001773 myeloid dendritic cell activation
GO:0001776 leukocyte homeostasis
GO:0001818 negative regulation of cytokine production
GO:0001819 positive regulation of cytokine production
GO:0001822 kidney development
GO:0001823 mesonephros development
GO:0001837 epithelial to mesenchymal transition
GO:0001838 embryonic epithelial tube formation
GO:0001841 neural tube formation
GO:0001843 neural tube closure
GO:0001889 liver development
GO:0001933 negative regulation of protein phosphorylation
GO:0001974 blood vessel remodeling
GO:0002028 regulation of sodium ion transport
GO:0002062 chondrocyte differentiation
GO:0002088 lens development in camera-type eye
GO:0002200 somatic diversification of immune receptors
GO:0002204 somatic recombination of immunoglobulin genes involved in immune response
GO:0002208 somatic diversification of immunoglobulins involved in immune response
GO:0002237 response to molecule of bacterial origin
GO:0002244 hematopoietic progenitor cell differentiation
GO:0002246 wound healing involved in inflammatory response
GO:0002248 connective tissue replacement involved in inflammatory response wound healing
GO:0002250 adaptive immune response
GO:0002260 lymphocyte homeostasis
GO:0002263 cell activation involved in immune response
GO:0002274 myeloid leukocyte activation
GO:0002285 lymphocyte activation involved in immune response
GO:0002312 B cell activation involved in immune response
GO:0002366 leukocyte activation involved in immune response
GO:0002367 cytokine production involved in immune response
GO:0002377 immunoglobulin production
GO:0002381 immunoglobulin production involved in immunoglobulin mediated immune response
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002507 tolerance induction
GO:0002513 tolerance induction to self antigen
GO:0002521 leukocyte differentiation
GO:0002562 somatic diversification of immune receptors via germline recombination within a single locus
GO:0002573 myeloid leukocyte differentiation
GO:0002576 platelet degranulation
GO:0002637 regulation of immunoglobulin production
GO:0002639 positive regulation of immunoglobulin production
GO:0002683 negative regulation of immune system process
GO:0002685 regulation of leukocyte migration
GO:0002687 positive regulation of leukocyte migration
GO:0002694 regulation of leukocyte activation
GO:0002695 negative regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002698 negative regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002700 regulation of production of molecular mediator of immune response
GO:0002701 negative regulation of production of molecular mediator of immune response
GO:0002702 positive regulation of production of molecular mediator of immune response
GO:0002703 regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002712 regulation of B cell mediated immunity
GO:0002714 positive regulation of B cell mediated immunity
GO:0002718 regulation of cytokine production involved in immune response
GO:0002719 negative regulation of cytokine production involved in immune response
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002889 regulation of immunoglobulin mediated immune response
GO:0002891 positive regulation of immunoglobulin mediated immune response
GO:0003007 heart morphogenesis
GO:0003013 circulatory system process
GO:0003018 vascular process in circulatory system
GO:0003170 heart valve development
GO:0003179 heart valve morphogenesis
GO:0003205 cardiac chamber development
GO:0003206 cardiac chamber morphogenesis
GO:0003208 cardiac ventricle morphogenesis
GO:0003229 ventricular cardiac muscle tissue development
GO:0003231 cardiac ventricle development
GO:0003401 axis elongation
GO:0005976 polysaccharide metabolic process
GO:0006022 aminoglycan metabolic process
GO:0006023 aminoglycan biosynthetic process
GO:0006024 glycosaminoglycan biosynthetic process
GO:0006026 aminoglycan catabolic process
GO:0006027 glycosaminoglycan catabolic process
GO:0006109 regulation of carbohydrate metabolic process
GO:0006164 purine nucleotide biosynthetic process
GO:0006260 DNA replication
GO:0006275 regulation of DNA replication
GO:0006310 DNA recombination
GO:0006417 regulation of translation
GO:0006470 protein dephosphorylation
GO:0006473 protein acetylation
GO:0006475 internal protein amino acid acetylation
GO:0006476 protein deacetylation
GO:0006606 protein import into nucleus
GO:0006611 protein export from nucleus
GO:0006644 phospholipid metabolic process
GO:0006754 ATP biosynthetic process
GO:0006801 superoxide metabolic process
GO:0006814 sodium ion transport
GO:0006816 calcium ion transport
GO:0006874 cellular calcium ion homeostasis
GO:0006875 cellular metal ion homeostasis
GO:0006887 exocytosis
GO:0006909 phagocytosis
GO:0006913 nucleocytoplasmic transport
GO:0007009 plasma membrane organization
GO:0007050 cell cycle arrest
GO:0007067 mitotic nuclear division
GO:0007088 regulation of mitotic nuclear division
GO:0007093 mitotic cell cycle checkpoint
GO:0007096 regulation of exit from mitosis
GO:0007159 leukocyte cell-cell adhesion
GO:0007162 negative regulation of cell adhesion
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007182 common-partner SMAD protein phosphorylation
GO:0007183 SMAD protein complex assembly
GO:0007184 SMAD protein import into nucleus
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007219 Notch signaling pathway
GO:0007272 ensheathment of neurons
GO:0007346 regulation of mitotic cell cycle
GO:0007405 neuroblast proliferation
GO:0007406 negative regulation of neuroblast proliferation
GO:0007423 sensory organ development
GO:0007431 salivary gland development
GO:0007435 salivary gland morphogenesis
GO:0007492 endoderm development
GO:0007507 heart development
GO:0007517 muscle organ development
GO:0007519 skeletal muscle tissue development
GO:0007565 female pregnancy
GO:0007568 aging
GO:0007584 response to nutrient
GO:0008015 blood circulation
GO:0008156 negative regulation of DNA replication
GO:0008354 germ cell migration
GO:0008366 axon ensheathment
GO:0009116 nucleoside metabolic process
GO:0009119 ribonucleoside metabolic process
GO:0009123 nucleoside monophosphate metabolic process
GO:0009124 nucleoside monophosphate biosynthetic process
GO:0009126 purine nucleoside monophosphate metabolic process
GO:0009127 purine nucleoside monophosphate biosynthetic process
GO:0009141 nucleoside triphosphate metabolic process
GO:0009142 nucleoside triphosphate biosynthetic process
GO:0009144 purine nucleoside triphosphate metabolic process
GO:0009145 purine nucleoside triphosphate biosynthetic process
GO:0009150 purine ribonucleotide metabolic process
GO:0009152 purine ribonucleotide biosynthetic process
GO:0009156 ribonucleoside monophosphate biosynthetic process
GO:0009161 ribonucleoside monophosphate metabolic process
GO:0009163 nucleoside biosynthetic process
GO:0009165 nucleotide biosynthetic process
GO:0009167 purine ribonucleoside monophosphate metabolic process
GO:0009168 purine ribonucleoside monophosphate biosynthetic process
GO:0009199 ribonucleoside triphosphate metabolic process
GO:0009201 ribonucleoside triphosphate biosynthetic process
GO:0009205 purine ribonucleoside triphosphate metabolic process
GO:0009206 purine ribonucleoside triphosphate biosynthetic process
GO:0009260 ribonucleotide biosynthetic process
GO:0009306 protein secretion
GO:0009314 response to radiation
GO:0009612 response to mechanical stimulus
GO:0009620 response to fungus
GO:0009743 response to carbohydrate
GO:0009746 response to hexose
GO:0009749 response to glucose
GO:0009814 defense response, incompatible interaction
GO:0009817 defense response to fungus, incompatible interaction
GO:0009991 response to extracellular stimulus
GO:0010001 glial cell differentiation
GO:0010171 body morphogenesis
GO:0010212 response to ionizing radiation
GO:0010458 exit from mitosis
GO:0010522 regulation of calcium ion transport into cytosol
GO:0010523 negative regulation of calcium ion transport into cytosol
GO:0010573 vascular endothelial growth factor production
GO:0010574 regulation of vascular endothelial growth factor production
GO:0010575 positive regulation of vascular endothelial growth factor production
GO:0010594 regulation of endothelial cell migration
GO:0010595 positive regulation of endothelial cell migration
GO:0010596 negative regulation of endothelial cell migration
GO:0010608 posttranscriptional regulation of gene expression
GO:0010631 epithelial cell migration
GO:0010632 regulation of epithelial cell migration
GO:0010633 negative regulation of epithelial cell migration
GO:0010634 positive regulation of epithelial cell migration
GO:0010712 regulation of collagen metabolic process
GO:0010714 positive regulation of collagen metabolic process
GO:0010715 regulation of extracellular matrix disassembly
GO:0010716 negative regulation of extracellular matrix disassembly
GO:0010717 regulation of epithelial to mesenchymal transition
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0010721 negative regulation of cell development
GO:0010742 macrophage derived foam cell differentiation
GO:0010761 fibroblast migration
GO:0010762 regulation of fibroblast migration
GO:0010763 positive regulation of fibroblast migration
GO:0010799 regulation of peptidyl-threonine phosphorylation
GO:0010800 positive regulation of peptidyl-threonine phosphorylation
GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0010934 macrophage cytokine production
GO:0010935 regulation of macrophage cytokine production
GO:0010936 negative regulation of macrophage cytokine production
GO:0010959 regulation of metal ion transport
GO:0014003 oligodendrocyte development
GO:0014020 primary neural tube formation
GO:0014706 striated muscle tissue development
GO:0015672 monovalent inorganic cation transport
GO:0016049 cell growth
GO:0016051 carbohydrate biosynthetic process
GO:0016064 immunoglobulin mediated immune response
GO:0016202 regulation of striated muscle tissue development
GO:0016311 dephosphorylation
GO:0016331 morphogenesis of embryonic epithelium
GO:0016441 posttranscriptional gene silencing
GO:0016444 somatic cell DNA recombination
GO:0016445 somatic diversification of immunoglobulins
GO:0016447 somatic recombination of immunoglobulin gene segments
GO:0016458 gene silencing
GO:0016570 histone modification
GO:0016573 histone acetylation
GO:0016575 histone deacetylation
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0017038 protein import
GO:0017148 negative regulation of translation
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018205 peptidyl-lysine modification
GO:0018209 peptidyl-serine modification
GO:0018210 peptidyl-threonine modification
GO:0018212 peptidyl-tyrosine modification
GO:0018393 internal peptidyl-lysine acetylation
GO:0018394 peptidyl-lysine acetylation
GO:0019048 modulation by virus of host morphology or physiology
GO:0019049 evasion or tolerance of host defenses by virus
GO:0019054 modulation by virus of host process
GO:0019216 regulation of lipid metabolic process
GO:0019724 B cell mediated immunity
GO:0021782 glial cell development
GO:0021915 neural tube development
GO:0022407 regulation of cell-cell adhesion
GO:0022408 negative regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0022412 cellular process involved in reproduction in multicellular organism
GO:0022612 gland morphogenesis
GO:0022617 extracellular matrix disassembly
GO:0030098 lymphocyte differentiation
GO:0030099 myeloid cell differentiation
GO:0030100 regulation of endocytosis
GO:0030198 extracellular matrix organization
GO:0030203 glycosaminoglycan metabolic process
GO:0030212 hyaluronan metabolic process
GO:0030213 hyaluronan biosynthetic process
GO:0030214 hyaluronan catabolic process
GO:0030217 T cell differentiation
GO:0030278 regulation of ossification
GO:0030279 negative regulation of ossification
GO:0030282 bone mineralization
GO:0030308 negative regulation of cell growth
GO:0030335 positive regulation of cell migration
GO:0030336 negative regulation of cell migration
GO:0030500 regulation of bone mineralization
GO:0030501 positive regulation of bone mineralization
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030879 mammary gland development
GO:0031047 gene silencing by RNA
GO:0031050 dsRNA fragmentation
GO:0031056 regulation of histone modification
GO:0031058 positive regulation of histone modification
GO:0031063 regulation of histone deacetylation
GO:0031065 positive regulation of histone deacetylation
GO:0031099 regeneration
GO:0031100 animal organ regeneration
GO:0031214 biomineral tissue development
GO:0031334 positive regulation of protein complex assembly
GO:0031349 positive regulation of defense response
GO:0031532 actin cytoskeleton reorganization
GO:0031536 positive regulation of exit from mitosis
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0031667 response to nutrient levels
GO:0031960 response to corticosteroid
GO:0032103 positive regulation of response to external stimulus
GO:0032355 response to estradiol
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032496 response to lipopolysaccharide
GO:0032570 response to progesterone
GO:0032620 interleukin-17 production
GO:0032627 interleukin-23 production
GO:0032660 regulation of interleukin-17 production
GO:0032667 regulation of interleukin-23 production
GO:0032700 negative regulation of interleukin-17 production
GO:0032740 positive regulation of interleukin-17 production
GO:0032801 receptor catabolic process
GO:0032844 regulation of homeostatic process
GO:0032845 negative regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0032881 regulation of polysaccharide metabolic process
GO:0032885 regulation of polysaccharide biosynthetic process
GO:0032928 regulation of superoxide anion generation
GO:0032930 positive regulation of superoxide anion generation
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032945 negative regulation of mononuclear cell proliferation
GO:0032956 regulation of actin cytoskeleton organization
GO:0032963 collagen metabolic process
GO:0032964 collagen biosynthetic process
GO:0032965 regulation of collagen biosynthetic process
GO:0032967 positive regulation of collagen biosynthetic process
GO:0032970 regulation of actin filament-based process
GO:0033135 regulation of peptidyl-serine phosphorylation
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033157 regulation of intracellular protein transport
GO:0033273 response to vitamin
GO:0033280 response to vitamin D
GO:0033674 positive regulation of kinase activity
GO:0034103 regulation of tissue remodeling
GO:0034248 regulation of cellular amide metabolic process
GO:0034249 negative regulation of cellular amide metabolic process
GO:0034250 positive regulation of cellular amide metabolic process
GO:0034284 response to monosaccharide
GO:0034330 cell junction organization
GO:0034405 response to fluid shear stress
GO:0034504 protein localization to nucleus
GO:0034616 response to laminar fluid shear stress
GO:0034762 regulation of transmembrane transport
GO:0034763 negative regulation of transmembrane transport
GO:0034765 regulation of ion transmembrane transport
GO:0034766 negative regulation of ion transmembrane transport
GO:0035051 cardiocyte differentiation
GO:0035065 regulation of histone acetylation
GO:0035066 positive regulation of histone acetylation
GO:0035148 tube formation
GO:0035194 posttranscriptional gene silencing by RNA
GO:0035195 gene silencing by miRNA
GO:0035196 production of miRNAs involved in gene silencing by miRNA
GO:0035239 tube morphogenesis
GO:0035272 exocrine system development
GO:0035303 regulation of dephosphorylation
GO:0035304 regulation of protein dephosphorylation
GO:0035306 positive regulation of dephosphorylation
GO:0035307 positive regulation of protein dephosphorylation
GO:0035601 protein deacylation
GO:0035821 modification of morphology or physiology of other organism
GO:0035902 response to immobilization stress
GO:0036293 response to decreased oxygen levels
GO:0036314 response to sterol
GO:0038127 ERBB signaling pathway
GO:0040013 negative regulation of locomotion
GO:0040017 positive regulation of locomotion
GO:0040029 regulation of gene expression, epigenetic
GO:0042063 gliogenesis
GO:0042098 T cell proliferation
GO:0042110 T cell activation
GO:0042113 B cell activation
GO:0042129 regulation of T cell proliferation
GO:0042130 negative regulation of T cell proliferation
GO:0042278 purine nucleoside metabolic process
GO:0042306 regulation of protein import into nucleus
GO:0042307 positive regulation of protein import into nucleus
GO:0042326 negative regulation of phosphorylation
GO:0042451 purine nucleoside biosynthetic process
GO:0042455 ribonucleoside biosynthetic process
GO:0042476 odontogenesis
GO:0042481 regulation of odontogenesis
GO:0042482 positive regulation of odontogenesis
GO:0042493 response to drug
GO:0042552 myelination
GO:0042554 superoxide anion generation
GO:0042692 muscle cell differentiation
GO:0042695 thelarche
GO:0043010 camera-type eye development
GO:0043011 myeloid dendritic cell differentiation
GO:0043029 T cell homeostasis
GO:0043062 extracellular structure organization
GO:0043112 receptor metabolic process
GO:0043113 receptor clustering
GO:0043114 regulation of vascular permeability
GO:0043117 positive regulation of vascular permeability
GO:0043254 regulation of protein complex assembly
GO:0043255 regulation of carbohydrate biosynthetic process
GO:0043271 negative regulation of ion transport
GO:0043331 response to dsRNA
GO:0043388 positive regulation of DNA binding
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043434 response to peptide hormone
GO:0043491 protein kinase B signaling
GO:0043534 blood vessel endothelial cell migration
GO:0043535 regulation of blood vessel endothelial cell migration
GO:0043536 positive regulation of blood vessel endothelial cell migration
GO:0043537 negative regulation of blood vessel endothelial cell migration
GO:0043542 endothelial cell migration
GO:0043543 protein acylation
GO:0043550 regulation of lipid kinase activity
GO:0043551 regulation of phosphatidylinositol 3-kinase activity
GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity
GO:0043583 ear development
GO:0043932 ossification involved in bone remodeling
GO:0044003 modification by symbiont of host morphology or physiology
GO:0044068 modulation by symbiont of host cellular process
GO:0044089 positive regulation of cellular component biogenesis
GO:0044236 multicellular organism metabolic process
GO:0044246 regulation of multicellular organismal metabolic process
GO:0044253 positive regulation of multicellular organismal metabolic process
GO:0044259 multicellular organismal macromolecule metabolic process
GO:0044413 avoidance of host defenses
GO:0044415 evasion or tolerance of host defenses
GO:0044416 induction by symbiont of host defense response
GO:0044706 multi-multicellular organism process
GO:0044723 single-organism carbohydrate metabolic process
GO:0044744 protein targeting to nucleus
GO:0044770 cell cycle phase transition
GO:0044772 mitotic cell cycle phase transition
GO:0045055 regulated exocytosis
GO:0045066 regulatory T cell differentiation
GO:0045136 development of secondary sexual characteristics
GO:0045190 isotype switching
GO:0045191 regulation of isotype switching
GO:0045216 cell-cell junction organization
GO:0045444 fat cell differentiation
GO:0045445 myoblast differentiation
GO:0045580 regulation of T cell differentiation
GO:0045582 positive regulation of T cell differentiation
GO:0045589 regulation of regulatory T cell differentiation
GO:0045591 positive regulation of regulatory T cell differentiation
GO:0045598 regulation of fat cell differentiation
GO:0045599 negative regulation of fat cell differentiation
GO:0045619 regulation of lymphocyte differentiation
GO:0045621 positive regulation of lymphocyte differentiation
GO:0045661 regulation of myoblast differentiation
GO:0045662 negative regulation of myoblast differentiation
GO:0045727 positive regulation of translation
GO:0045778 positive regulation of ossification
GO:0045785 positive regulation of cell adhesion
GO:0045786 negative regulation of cell cycle
GO:0045787 positive regulation of cell cycle
GO:0045806 negative regulation of endocytosis
GO:0045830 positive regulation of isotype switching
GO:0045834 positive regulation of lipid metabolic process
GO:0045840 positive regulation of mitotic nuclear division
GO:0045843 negative regulation of striated muscle tissue development
GO:0045844 positive regulation of striated muscle tissue development
GO:0045860 positive regulation of protein kinase activity
GO:0045911 positive regulation of DNA recombination
GO:0045912 negative regulation of carbohydrate metabolic process
GO:0045926 negative regulation of growth
GO:0045930 negative regulation of mitotic cell cycle
GO:0045931 positive regulation of mitotic cell cycle
GO:0046034 ATP metabolic process
GO:0046128 purine ribonucleoside metabolic process
GO:0046129 purine ribonucleoside biosynthetic process
GO:0046390 ribose phosphate biosynthetic process
GO:0046543 development of secondary female sexual characteristics
GO:0046651 lymphocyte proliferation
GO:0046730 induction of host immune response by virus
GO:0046732 active induction of host immune response by virus
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046824 positive regulation of nucleocytoplasmic transport
GO:0046849 bone remodeling
GO:0048144 fibroblast proliferation
GO:0048145 regulation of fibroblast proliferation
GO:0048146 positive regulation of fibroblast proliferation
GO:0048290 isotype switching to IgA isotypes
GO:0048296 regulation of isotype switching to IgA isotypes
GO:0048298 positive regulation of isotype switching to IgA isotypes
GO:0048514 blood vessel morphogenesis
GO:0048535 lymph node development
GO:0048545 response to steroid hormone
GO:0048565 digestive tract development
GO:0048568 embryonic organ development
GO:0048634 regulation of muscle organ development
GO:0048635 negative regulation of muscle organ development
GO:0048636 positive regulation of muscle organ development
GO:0048641 regulation of skeletal muscle tissue development
GO:0048642 negative regulation of skeletal muscle tissue development
GO:0048644 muscle organ morphogenesis
GO:0048705 skeletal system morphogenesis
GO:0048709 oligodendrocyte differentiation
GO:0048732 gland development
GO:0048738 cardiac muscle tissue development
GO:0048754 branching morphogenesis of an epithelial tube
GO:0048762 mesenchymal cell differentiation
GO:0048771 tissue remodeling
GO:0048839 inner ear development
GO:0048872 homeostasis of number of cells
GO:0050670 regulation of lymphocyte proliferation
GO:0050672 negative regulation of lymphocyte proliferation
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050679 positive regulation of epithelial cell proliferation
GO:0050680 negative regulation of epithelial cell proliferation
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050764 regulation of phagocytosis
GO:0050765 negative regulation of phagocytosis
GO:0050768 negative regulation of neurogenesis
GO:0050777 negative regulation of immune response
GO:0050832 defense response to fungus
GO:0050863 regulation of T cell activation
GO:0050864 regulation of B cell activation
GO:0050865 regulation of cell activation
GO:0050866 negative regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050868 negative regulation of T cell activation
GO:0050870 positive regulation of T cell activation
GO:0050871 positive regulation of B cell activation
GO:0050900 leukocyte migration
GO:0050920 regulation of chemotaxis
GO:0050921 positive regulation of chemotaxis
GO:0051047 positive regulation of secretion
GO:0051051 negative regulation of transport
GO:0051052 regulation of DNA metabolic process
GO:0051053 negative regulation of DNA metabolic process
GO:0051054 positive regulation of DNA metabolic process
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051098 regulation of binding
GO:0051099 positive regulation of binding
GO:0051101 regulation of DNA binding
GO:0051145 smooth muscle cell differentiation
GO:0051146 striated muscle cell differentiation
GO:0051147 regulation of muscle cell differentiation
GO:0051148 negative regulation of muscle cell differentiation
GO:0051149 positive regulation of muscle cell differentiation
GO:0051150 regulation of smooth muscle cell differentiation
GO:0051152 positive regulation of smooth muscle cell differentiation
GO:0051153 regulation of striated muscle cell differentiation
GO:0051155 positive regulation of striated muscle cell differentiation
GO:0051168 nuclear export
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051208 sequestering of calcium ion
GO:0051209 release of sequestered calcium ion into cytosol
GO:0051216 cartilage development
GO:0051222 positive regulation of protein transport
GO:0051235 maintenance of location
GO:0051238 sequestering of metal ion
GO:0051249 regulation of lymphocyte activation
GO:0051250 negative regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051271 negative regulation of cellular component movement
GO:0051272 positive regulation of cellular component movement
GO:0051279 regulation of release of sequestered calcium ion into cytosol
GO:0051280 negative regulation of release of sequestered calcium ion into cytosol
GO:0051282 regulation of sequestering of calcium ion
GO:0051283 negative regulation of sequestering of calcium ion
GO:0051284 positive regulation of sequestering of calcium ion
GO:0051302 regulation of cell division
GO:0051384 response to glucocorticoid
GO:0051480 regulation of cytosolic calcium ion concentration
GO:0051493 regulation of cytoskeleton organization
GO:0051668 localization within membrane
GO:0051701 interaction with host
GO:0051781 positive regulation of cell division
GO:0051783 regulation of nuclear division
GO:0051785 positive regulation of nuclear division
GO:0051817 modification of morphology or physiology of other organism involved in symbiotic interaction
GO:0051832 avoidance of defenses of other organism involved in symbiotic interaction
GO:0051834 evasion or tolerance of defenses of other organism involved in symbiotic interaction
GO:0051896 regulation of protein kinase B signaling
GO:0051897 positive regulation of protein kinase B signaling
GO:0051924 regulation of calcium ion transport
GO:0051926 negative regulation of calcium ion transport
GO:0051961 negative regulation of nervous system development
GO:0052031 modulation by symbiont of host defense response
GO:0052173 response to defenses of other organism involved in symbiotic interaction
GO:0052200 response to host defenses
GO:0052251 induction by organism of defense response of other organism involved in symbiotic interaction
GO:0052255 modulation by organism of defense response of other organism involved in symbiotic interaction
GO:0052509 positive regulation by symbiont of host defense response
GO:0052510 positive regulation by organism of defense response of other organism involved in symbiotic interaction
GO:0052552 modulation by organism of immune response of other organism involved in symbiotic interaction
GO:0052553 modulation by symbiont of host immune response
GO:0052564 response to immune response of other organism involved in symbiotic interaction
GO:0052572 response to host immune response
GO:0055007 cardiac muscle cell differentiation
GO:0055008 cardiac muscle tissue morphogenesis
GO:0055010 ventricular cardiac muscle tissue morphogenesis
GO:0055024 regulation of cardiac muscle tissue development
GO:0055025 positive regulation of cardiac muscle tissue development
GO:0055074 calcium ion homeostasis
GO:0055123 digestive system development
GO:0060147 regulation of posttranscriptional gene silencing
GO:0060149 negative regulation of posttranscriptional gene silencing
GO:0060312 regulation of blood vessel remodeling
GO:0060323 head morphogenesis
GO:0060324 face development
GO:0060325 face morphogenesis
GO:0060348 bone development
GO:0060349 bone morphogenesis
GO:0060363 cranial suture morphogenesis
GO:0060364 frontal suture morphogenesis
GO:0060389 pathway-restricted SMAD protein phosphorylation
GO:0060390 regulation of SMAD protein import into nucleus
GO:0060391 positive regulation of SMAD protein import into nucleus
GO:0060393 regulation of pathway-restricted SMAD protein phosphorylation
GO:0060395 SMAD protein signal transduction
GO:0060401 cytosolic calcium ion transport
GO:0060402 calcium ion transport into cytosol
GO:0060415 muscle tissue morphogenesis
GO:0060443 mammary gland morphogenesis
GO:0060444 branching involved in mammary gland duct morphogenesis
GO:0060485 mesenchyme development
GO:0060537 muscle tissue development
GO:0060538 skeletal muscle organ development
GO:0060560 developmental growth involved in morphogenesis
GO:0060562 epithelial tube morphogenesis
GO:0060602 branch elongation of an epithelium
GO:0060603 mammary gland duct morphogenesis
GO:0060606 tube closure
GO:0060627 regulation of vesicle-mediated transport
GO:0060675 ureteric bud morphogenesis
GO:0060688 regulation of morphogenesis of a branching structure
GO:0060744 mammary gland branching involved in thelarche
GO:0060751 branch elongation involved in mammary gland duct branching
GO:0060762 regulation of branching involved in mammary gland duct morphogenesis
GO:0060964 regulation of gene silencing by miRNA
GO:0060965 negative regulation of gene silencing by miRNA
GO:0060966 regulation of gene silencing by RNA
GO:0060967 negative regulation of gene silencing by RNA
GO:0060968 regulation of gene silencing
GO:0060969 negative regulation of gene silencing
GO:0060993 kidney morphogenesis
GO:0061008 hepaticobiliary system development
GO:0061035 regulation of cartilage development
GO:0061082 myeloid leukocyte cytokine production
GO:0061138 morphogenesis of a branching epithelium
GO:0061180 mammary gland epithelium development
GO:0061213 positive regulation of mesonephros development
GO:0061217 regulation of mesonephros development
GO:0061311 cell surface receptor signaling pathway involved in heart development
GO:0061326 renal tubule development
GO:0061333 renal tubule morphogenesis
GO:0061351 neural precursor cell proliferation
GO:0061448 connective tissue development
GO:0061614 pri-miRNA transcription from RNA polymerase II promoter
GO:0070167 regulation of biomineral tissue development
GO:0070169 positive regulation of biomineral tissue development
GO:0070306 lens fiber cell differentiation
GO:0070482 response to oxygen levels
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070509 calcium ion import
GO:0070588 calcium ion transmembrane transport
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070664 negative regulation of leukocyte proliferation
GO:0070723 response to cholesterol
GO:0070838 divalent metal ion transport
GO:0070918 production of small RNA involved in gene silencing by RNA
GO:0070920 regulation of production of small RNA involved in gene silencing by RNA
GO:0071156 regulation of cell cycle arrest
GO:0071158 positive regulation of cell cycle arrest
GO:0071214 cellular response to abiotic stimulus
GO:0071216 cellular response to biotic stimulus
GO:0071219 cellular response to molecule of bacterial origin
GO:0071222 cellular response to lipopolysaccharide
GO:0071260 cellular response to mechanical stimulus
GO:0071359 cellular response to dsRNA
GO:0071375 cellular response to peptide hormone stimulus
GO:0071383 cellular response to steroid hormone stimulus
GO:0071384 cellular response to corticosteroid stimulus
GO:0071385 cellular response to glucocorticoid stimulus
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0071417 cellular response to organonitrogen compound
GO:0071478 cellular response to radiation
GO:0071479 cellular response to ionizing radiation
GO:0071496 cellular response to external stimulus
GO:0071548 response to dexamethasone
GO:0071549 cellular response to dexamethasone stimulus
GO:0071559 response to transforming growth factor beta
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0071593 lymphocyte aggregation
GO:0071674 mononuclear cell migration
GO:0071675 regulation of mononuclear cell migration
GO:0071677 positive regulation of mononuclear cell migration
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0072001 renal system development
GO:0072006 nephron development
GO:0072009 nephron epithelium development
GO:0072028 nephron morphogenesis
GO:0072073 kidney epithelium development
GO:0072078 nephron tubule morphogenesis
GO:0072080 nephron tubule development
GO:0072088 nephron epithelium morphogenesis
GO:0072089 stem cell proliferation
GO:0072091 regulation of stem cell proliferation
GO:0072163 mesonephric epithelium development
GO:0072164 mesonephric tubule development
GO:0072171 mesonephric tubule morphogenesis
GO:0072175 epithelial tube formation
GO:0072503 cellular divalent inorganic cation homeostasis
GO:0072507 divalent inorganic cation homeostasis
GO:0072511 divalent inorganic cation transport
GO:0072522 purine-containing compound biosynthetic process
GO:0072593 reactive oxygen species metabolic process
GO:0072657 protein localization to membrane
GO:0072659 protein localization to plasma membrane
GO:0075136 response to host
GO:0075528 modulation by virus of host immune response
GO:0085029 extracellular matrix assembly
GO:0090068 positive regulation of cell cycle process
GO:0090077 foam cell differentiation
GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090100 positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090101 negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:0090183 regulation of kidney development
GO:0090184 positive regulation of kidney development
GO:0090189 regulation of branching involved in ureteric bud morphogenesis
GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis
GO:0090218 positive regulation of lipid kinase activity
GO:0090279 regulation of calcium ion import
GO:0090281 negative regulation of calcium ion import
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0090288 negative regulation of cellular response to growth factor stimulus
GO:0090311 regulation of protein deacetylation
GO:0090312 positive regulation of protein deacetylation
GO:0090316 positive regulation of intracellular protein transport
GO:0090322 regulation of superoxide metabolic process
GO:0090594 inflammatory response to wounding
GO:0097028 dendritic cell differentiation
GO:0097094 craniofacial suture morphogenesis
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097305 response to alcohol
GO:0097421 liver regeneration
GO:0097553 calcium ion transmembrane import into cytosol
GO:0097709 connective tissue replacement
GO:0098542 defense response to other organism
GO:0098732 macromolecule deacylation
GO:1900125 regulation of hyaluronan biosynthetic process
GO:1900126 negative regulation of hyaluronan biosynthetic process
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1901136 carbohydrate derivative catabolic process
GO:1901201 regulation of extracellular matrix assembly
GO:1901203 positive regulation of extracellular matrix assembly
GO:1901293 nucleoside phosphate biosynthetic process
GO:1901565 organonitrogen compound catabolic process
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1901654 response to ketone
GO:1901655 cellular response to ketone
GO:1901657 glycosyl compound metabolic process
GO:1901659 glycosyl compound biosynthetic process
GO:1901664 regulation of NAD+ ADP-ribosyltransferase activity
GO:1901666 positive regulation of NAD+ ADP-ribosyltransferase activity
GO:1901861 regulation of muscle tissue development
GO:1901862 negative regulation of muscle tissue development
GO:1901863 positive regulation of muscle tissue development
GO:1901983 regulation of protein acetylation
GO:1901985 positive regulation of protein acetylation
GO:1901987 regulation of cell cycle phase transition
GO:1901989 positive regulation of cell cycle phase transition
GO:1901990 regulation of mitotic cell cycle phase transition
GO:1901992 positive regulation of mitotic cell cycle phase transition
GO:1902105 regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1902275 regulation of chromatin organization
GO:1902593 single-organism nuclear import
GO:1902656 calcium ion import into cytosol
GO:1902692 regulation of neuroblast proliferation
GO:1902893 regulation of pri-miRNA transcription from RNA polymerase II promoter
GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903038 negative regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903053 regulation of extracellular matrix organization
GO:1903054 negative regulation of extracellular matrix organization
GO:1903055 positive regulation of extracellular matrix organization
GO:1903076 regulation of protein localization to plasma membrane
GO:1903077 negative regulation of protein localization to plasma membrane
GO:1903169 regulation of calcium ion transmembrane transport
GO:1903170 negative regulation of calcium ion transmembrane transport
GO:1903510 mucopolysaccharide metabolic process
GO:1903532 positive regulation of secretion by cell
GO:1903533 regulation of protein targeting
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1903725 regulation of phospholipid metabolic process
GO:1903727 positive regulation of phospholipid metabolic process
GO:1903729 regulation of plasma membrane organization
GO:1903798 regulation of production of miRNAs involved in gene silencing by miRNA
GO:1903799 negative regulation of production of miRNAs involved in gene silencing by miRNA
GO:1903828 negative regulation of cellular protein localization
GO:1903829 positive regulation of cellular protein localization
GO:1903844 regulation of cellular response to transforming growth factor beta stimulus
GO:1903845 negative regulation of cellular response to transforming growth factor beta stimulus
GO:1903909 regulation of receptor clustering
GO:1903911 positive regulation of receptor clustering
GO:1904062 regulation of cation transmembrane transport
GO:1904063 negative regulation of cation transmembrane transport
GO:1904375 regulation of protein localization to cell periphery
GO:1904376 negative regulation of protein localization to cell periphery
GO:1904589 regulation of protein import
GO:1904591 positive regulation of protein import
GO:1904888 cranial skeletal system development
GO:1904951 positive regulation of establishment of protein localization
GO:1905207 regulation of cardiocyte differentiation
GO:1905209 positive regulation of cardiocyte differentiation
GO:1905269 positive regulation of chromatin organization
GO:1905313 transforming growth factor beta receptor signaling pathway involved in heart development
GO:1905330 regulation of morphogenesis of an epithelium
GO:1905332 positive regulation of morphogenesis of an epithelium
GO:1990314 cellular response to insulin-like growth factor stimulus
GO:1990402 embryonic liver development
GO:1990778 protein localization to cell periphery
GO:2000021 regulation of ion homeostasis
GO:2000027 regulation of organ morphogenesis
GO:2000146 negative regulation of cell motility
GO:2000147 positive regulation of cell motility
GO:2000177 regulation of neural precursor cell proliferation
GO:2000178 negative regulation of neural precursor cell proliferation
GO:2000249 regulation of actin cytoskeleton reorganization
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
GO:2000647 negative regulation of stem cell proliferation
GO:2000677 regulation of transcription regulatory region DNA binding
GO:2000679 positive regulation of transcription regulatory region DNA binding
GO:2000725 regulation of cardiac muscle cell differentiation
GO:2000727 positive regulation of cardiac muscle cell differentiation
GO:2000756 regulation of peptidyl-lysine acetylation
GO:2000758 positive regulation of peptidyl-lysine acetylation
Molecular Function GO:0001948 glycoprotein binding
GO:0003823 antigen binding
GO:0005114 type II transforming growth factor beta receptor binding
GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0005160 transforming growth factor beta receptor binding
GO:0008047 enzyme activator activity
GO:0008083 growth factor activity
GO:0019207 kinase regulator activity
GO:0019209 kinase activator activity
GO:0019887 protein kinase regulator activity
GO:0030295 protein kinase activator activity
GO:0034713 type I transforming growth factor beta receptor binding
GO:0034714 type III transforming growth factor beta receptor binding
GO:0043539 protein serine/threonine kinase activator activity
GO:0046982 protein heterodimerization activity
GO:0047485 protein N-terminus binding
Cellular Component GO:0005578 proteinaceous extracellular matrix
GO:0005796 Golgi lumen
GO:0005902 microvillus
GO:0030141 secretory granule
GO:0030424 axon
GO:0031091 platelet alpha granule
GO:0031093 platelet alpha granule lumen
GO:0031983 vesicle lumen
GO:0034774 secretory granule lumen
GO:0043025 neuronal cell body
GO:0044297 cell body
GO:0060205 cytoplasmic membrane-bounded vesicle lumen
GO:0072562 blood microparticle
GO:0098858 actin-based cell projection
GO:0099503 secretory vesicle
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04060 Cytokine-cytokine receptor interaction
hsa04068 FoxO signaling pathway
hsa04110 Cell cycle
hsa04144 Endocytosis
hsa04350 TGF-beta signaling pathway
hsa04380 Osteoclast differentiation
hsa04390 Hippo signaling pathway
hsa04672 Intestinal immune network for IgA production
Reactome R-HSA-202733: Cell surface interactions at the vascular wall
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-5688426: Deubiquitination
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-2173788: Downregulation of TGF-beta receptor signaling
R-HSA-3000178: ECM proteoglycans
R-HSA-1566948: Elastic fibre formation
R-HSA-1474244: Extracellular matrix organization
R-HSA-109582: Hemostasis
R-HSA-168253: Host Interactions with Influenza Factors
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-168254: Influenza Infection
R-HSA-168277: Influenza Virus Induced Apoptosis
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-3304349: Loss of Function of SMAD2/3 in Cancer
R-HSA-3656534: Loss of Function of TGFBR1 in Cancer
R-HSA-3642278: Loss of Function of TGFBR2 in Cancer
R-HSA-392499: Metabolism of proteins
R-HSA-2129379: Molecules associated with elastic fibres
R-HSA-3000171: Non-integrin membrane-ECM interactions
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-597592: Post-translational protein modification
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
R-HSA-3315487: SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-3304356: SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-170834: Signaling by TGF-beta Receptor Complex
R-HSA-3304351: Signaling by TGF-beta Receptor Complex in Cancer
R-HSA-3000170: Syndecan interactions
R-HSA-2173789: TGF-beta receptor signaling activates SMADs
R-HSA-2173791: TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-3656532: TGFBR1 KD Mutants in Cancer
R-HSA-3656535: TGFBR1 LBD Mutants in Cancer
R-HSA-3645790: TGFBR2 Kinase Domain Mutants in Cancer
R-HSA-3642279: TGFBR2 MSI Frameshift Mutants in Cancer
R-HSA-381340: Transcriptional regulation of white adipocyte differentiation
R-HSA-5689603: UCH proteinases
Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TGFB1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between TGFB1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26740106Head and Neck Squamous Cell CarcinomaInhibit immunity (T cell function)Similarly, knockdown of Sema4D in an HNSCC cell line resulted in a loss of MDSC function as shown by a decrease in the production of the immune-suppressive cytokines arginase-1, TGF-β, and IL-10 by MDSC, concomitant with recovery of T cell proliferation and IFN-γ production following stimulation of CD3/CD28.
26980767Pancreatic CarcinomaInhibit immunityTGFβ Signaling in the Pancreatic Tumor Microenvironment Promotes Fibrosis and Immune Evasion to Facilitate Tumorigenesis.
27197181Breast CarcinomaInhibit immunity (T cell function)Ly6E/K Signaling to TGFβ Promotes Breast Cancer Progression, Immune Escape, and Drug Resistance. Increased expression of Ly6K/E also correlated with increased expression of the immune checkpoint molecules PDL1 and CTLA4, increased tumor-infiltrating T regulatory cells, and decreased natural killer (NK) cell activation.
26921343Lung CarcinomaPromote immunity (infiltration, T cell function)Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Mechanistic investigations revealed that TGFβ bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrin-linked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation, thereby initiating integrin inside-out signaling.
26880715Lung CarcinomaInhibit immunity (T cell function)Overexpression of the mutant KRAS(G12V)gene in wild-type KRAS tumor cells led to regulatory T-cell (Treg) induction. We also demonstrate that mutant KRAS induces the secretion of IL10 and transforming growth factor-β1 (both required for Treg induction) by tumor cells through the activation of the MEK-ERK-AP1 pathway.
26139534MelanomaInhibit immunity (T cell function)Therefore, the melanoma microenvironment contributes to skewing of CD8 T cell differentiation programs, in part by TGFβ/IL-6-mediated induction of Maf.
25924227MelanomaInhibit immunity (T cell function)Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression.
25744719Lung CarcinomaInhibit immunity (T cell function)We conclude that pulmonary exposure to SWCNT favors the formation of a niche that supports ingrowth of lung carcinoma in vivo via activation of TGFβ production by SWCNT-attracted and -presensitized MDSC.
25347474Lung CarcinomaInhibit immunity (T cell function)We determined that tumor-derived TGF-β directly suppresses CTL immune function by elevating miR-23a and downregulating BLIMP-1. Functional blocking of miR-23a in human CTLs enhanced granzyme B expression, and in mice with established tumors, immunotherapy with just a small number of tumor-specific CTLs in which miR-23a was inhibited robustly hindered tumor progression.
22615204Hepatocellular CarcinomaInhibit immunity (T cell function)Suppression of CD8(+) T cells by CCR4(+)CCR6(+)Th17 cells was partially dependent on TGF-β, because neutralization of TGF-β in cocultures reversed their suppressor function.
24586048Lung CarcinomaInhibit immunity (NK cell function)Instead, TGF-β depleted DNAX activating protein 12 kDa (DAP12), which is critical for surface NK receptor stabilization and downstream signal transduction. Mechanistic analysis revealed that TGF-β induced microRNA (miR)-183 to repress DAP12 transcription/translation.
24569779B-Cell Non-Hodgkin LymphomaInhibit immunity (T cell function)TGF-β upregulates CD70 expression and induces exhaustion of effector memory T cells in B-cell non-Hodgkin's lymphoma.
29443964Colorectal carcinoma, hepatocellular carcinomaInhibit immunity (T cell function); immunotherapy targetInstead, particular features of the tumour microenvironment, such as lack of T-cell infiltration, low type 1 T-helper cell (TH1) activity and reduced immune cytotoxicity or increased TGFβ levels predict adverse outcomes in patients with colorectal cancer. In mice with progressive liver metastatic disease, blockade of TGFβ signalling rendered tumours susceptible to anti-PD-1-PD-L1 therapy. Immunotherapies directed against TGFβ signalling may therefore have broad applications in treating patients with advanced colorectal cancer.
29443960Urethral urothelial carcinomaInhibit immunity (T cell function); immunotherapy targetLack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8+ T cells from the tumour parenchyma that were instead found in the fibroblast- and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-tumour immunity and tumour regression.
28574228CholangiocarcinomaInhibit immunity (T cell function)Our findings further indicated that CCA cells with EMT-like features appear to generate immunosuppressive natural T regulatory-like cluster of differentiation 4-positive (CD4+)CD25-cells rather than to increase CD4+CD25+natural T regulatory cells, in part by mediating T regulatory-inducible cytokines such as transforming growth factor β1 and interleukin 2.These results demonstrate that aPKC-ι promotes EMT and induces immunosuppression through the aPKC-ι/P-Sp1/Snail signaling pathway and may be a potential therapeutic target for CCA.
28497804GliomaInhibit immunity (T cell function); essential for immunotherapyHowever, some preclinical trial data suggest that addition of immunomodulatory reagents such as immune checkpoint inhibitors, transforming growth factor-β inhibitors, signal transducer and activator of transcription 3 inhibitors, or modifiers of tryptophan metabolism could augment the therapeutic activity of vaccination and overcome glioma-associated immunosuppression.
23389942Breast CarcinomaInhibit immunity (T cell function)We demonstrate that besides IFN-α, the production by Toll-like receptor (TLR)-activated healthy pDC of IFN-β and TNF-α but not IP-10/CXCL10 nor MIP1-α/CCL3 is impaired by the breast tumor environment. Indeed, recombinant TGF-β1 and TNF-α synergistically blocked IFN-α production of TLR-activated pDC, and neutralization of TGF-β and TNF-α in tumor-derived supernatants restored pDCs' IFN-α production.Importantly, we identified TGF-β and TNF-α as major soluble factors involved in TApDC functional alteration.
21207371Colon CarcinomaInhibit immunity (T cell function)Here we show that CD103, an integrin mediating lymphocyte retention in epithelial tissues, is expressed at high levels on tumor-infiltrating FoxP3+ Treg in several types of murine cancer. In the CT26 model of colon cancer up to 90% of the intratumoral FoxP3+ cells expressed CD103 compared to less than 20% in lymphoid organs. CD103+ Treg suppressed T effector cell activation more strongly than CD103(neg) Treg. Expression of CD103 on Treg closely correlated with intratumoral levels of transforming growth factor β (TGF-β) and could be induced in a TGF-β-dependent manner by tumor cell lines. In vivo, gene silencing of TGF-β reduced the frequency of CD103+ Treg, demonstrating that CD103 expression on tumor-infiltrating Treg is driven by intratumoral TGF-β.
21159663MelanomaInhibit immunityInduction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in melanoma enhances tumor infiltration and immunosuppression.
19491278LymphomaInhibit immunity (T cell function)For inhibition of TGF-beta-mediated immunosuppression in DLNs, C57BL/6 mice subcutaneously bearing E.G7 tumors were administered plasmid DNA encoding the extracellular domain of TGF-beta type II receptor fused to the human IgG heavy chain (TGFR DNA) i.m. In DLNs, inhibition of TGF-beta suppressed the proliferation of regulatory T cells and increased the number of tumor antigen-specific CD4(+) or CD8(+) cells producing IFN-gamma.
16788095LeukemiaPromote immunity (T cell function)CD8+ memory T cells, as defined by CD44(hi) surface expression, are dependent on IL-15 as a positive regulator of their homeostatic maintenance. Manipulation of IL-15 signaling through gene aberration, overexpression, or receptor alterations has been shown to dramatically affect T-cell homeostasis, with overexpression leading to fatal leukemia. Here we show that TGF-beta is the critical negative regulator of murine CD8+ memory T-cell homeostasis with direct opposition to the positive effects of IL-15.
16751376Breast CarcinomaInhibit immunity (T cell function)A single intratumoral injection of IL-12 and GM-CSF-encapsulated microspheres induces the complete regression of advanced spontaneous tumors in her-2/neu transgenic mice. Posttherapy molecular analysis of immune activation/suppression markers within the tumor microenvironment demonstrated a dramatic up-regulation of IFN-gamma and a concomitant down-regulation of Forkhead/winged-helix protein 3 (Foxp3), TGFbeta, and IL-10 expression.
16540672Lung CarcinomaInhibit immunityA single intratracheal administration of CCL21 gene-modified dendritic cells (DC-AdCCL21) led to a marked reduction in tumor burden with extensive mononuclear cell infiltration of the tumors. The reduction in tumor burden was accompanied by the enhanced elaboration of type 1 cytokines [IFN-gamma, interleukin (IL)-12, and granulocyte macrophage colony-stimulating factor] and antiangiogenic chemokines (CXCL9 and CXCL10) but a concomitant decrease in the immunosuppressive molecules (IL-10, transforming growth factor-beta, prostaglandin E(2)) in the tumor microenvironment. The DC-AdCCL21 therapy group revealed a significantly greater frequency of tumor-specific T cells releasing IFN-gamma compared with the controls.
27488528Chronic Lymphocytic LeukemiaPromote immunityNotably, in progressive CLL, splenic neutrophils were observed to differentiate toward a B-cell helper phenotype, a process promoted by the induction of leukemia-associated IL10 and TGFβ. Our results suggest that targeting aberrant neutrophil differentiation and restoring myeloid cell homeostasis could limit the formation of survival niches for CLL cells.
23754772MelanomaInhibit immunity (T cell function)To that end, T cells purified from healthy donors and from vaccinated-melanoma patients were transduced to express high levels of constitutive 4-1BB. In addition, these cells expanded and proliferated at a higher rate, expressed heightened levels of the antiapoptotic molecule Bcl(XL) and were also relatively insensitive to immunosuppression mediated by transforming growth factor-β, compared to control cells. We also show that 4-1BBL expression on the target cell is essential to 4-1BB-mediated functional improvement. Overall, we conclude that the modification of human T cells with 4-1BB yields enhanced antitumor function which may have important applications in therapies based on the genetic modification of patient lymphocytes.
22282655Colorectal CarcinomaInhibit immunity (T cell function)We found that higher levels of CCL5 expression in human and murine colon tumor cells correlated with higher levels of apoptosis of CD8+ T cells and infiltration of T-regulatory cells (T(reg)). We also found tumor growth to be diminished in mice lacking CCR5, a CCL5 receptor, where a similar decrease in both T(reg) cell infiltration and CD8(+) T-cell apoptosis was noted. TGF-β signaling blockade diminished apoptosis of CD8(+) T cells, implicating TGF-β as an effector of CCL5 action. In support of this concept, CCL5 failed to enhance the production of TGF-β by CCR5-deficient T(reg) or to enhance their cytotoxic effects against CD8(+) T cells.
17440061GlioblastomaInhibit immunity (NK cell function)Lectin-like transcript-1 (LLT1) is a newly identified ligand for the inhibitory natural killer (NK) cell receptor CD161. Here, we report that glioma cells express LLT1 mRNA and protein in vitro and in vivo, whereas expression levels in normal brain are low. LLT1 expression in human gliomas increases with the WHO grade of malignancy. We further show that transforming growth factor-beta (TGF-beta) up-regulates the expression of LLT1 in glioma cells.
20858897Skin Basal Cell CarcinomaInhibit immunity (T cell function)Furthermore, inhibition of TGFβ signaling by TGFβ receptor I inhibitor SD208 significantly reduced tumor area in K14cre/R26SmoM2 mice. Tumor shrinkage in mice was associated with an increased number of lymphocytes, suggesting an immune suppression role of TGFβ signaling.
19861464GliomaInhibit immunity (T cell function)Flow cytometric analyses of brain-infiltrating lymphocytes revealed that 1D11 treatment suppressed phosphorylation of Smad2, increased GAA-reactive/IFN-gamma-producing CD8(+) T cells, and reduced CD4(+)/FoxP3(+) T(reg) cells in the glioma microenvironment. Neutralization of TGF-beta also upregulated plasma levels of interleukin-12, macrophage inflammatory protein-1 alpha, and IFN-inducible protein-10, suggesting a systemic promotion of type-1 cytokine/chemokine production. Furthermore, 1D11 treatment upregulated plasma interleukin-15 levels and promoted the persistence of GAA-reactive CD8(+) T cells in glioma-bearing mice.
19830696Colon CarcinomaInhibit immunity (T cell function)However, tumor growth was inhibited significantly more in vaccinated mice treated with anti-TGF-beta antibodies compared to vaccinated mice without anti-TGF-beta, suggesting that anti-TGF-beta synergistically enhanced irradiated tumor vaccine efficacy.
19109155Hepatocellular CarcinomaInhibit immunity (T cell function)Furthermore, membrane-bound TGF-beta1 on MDSC is responsible for MDSC-mediated suppression of NK cells. The impaired function of hepatic NK cells in orthotopic liver cancer-bearing mice could be restored by depletion of MDSC, but not regulatory T cells. Therefore, cancer-expanded MDSC can induce anergy of NK cells via membrane-bound TGF-beta1. MDSC, but not regulatory T cells, are main negative regulator of hepatic NK cell function in tumor-bearing host.
19109141Hepatocellular Carcinoma; Lung Carcinoma; MelanomaInhibit immunity (T cell function)Interestingly, the fixed CD69(+)CD4(+)CD25(-) T cells still have suppressive activity, and neutralizing Abs against TGF-beta1 can block their suppressive activity. We found that CD69(+)CD4(+)CD25(-) T cells express membrane-bound TGF-beta1, which mediates suppression of T cell proliferation. Furthermore, engagement of CD69 maintains high expression of membrane-bound TGF-beta1 on CD69(+)CD4(+)CD25(-) T cells via ERK activation.
19022917Colorectal CarcinomaInhibit immunity (T cell function)Moreover, T8reg were able to suppress CD4(+)CD25(-) T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumour-infiltrating T8reg have strong suppressive capacities. T8reg numbers correlated with the tumour stage and with micro-invasive status. Finally, interleukin 6 and TGF beta 1 synergistically induced the generation of CD8(+)CD25(+)Foxp3(+) T cells ex vivo.
17768418Skin CarcinomaInhibit immunity (infitration)Flow cytometry was used to show that TGFbeta-mediated tumour progression was accompanied by an increase in tumour-associated macrophages (TAM) and a decrease in tumour-infiltrating dendritic cells (DCs). TAM in TGFbeta-secreting tumours expressed lower levels of major histocompatibility complex II and CD86 compared to DC in control tumours and had a high phagocytic capacity as measured by uptake of latex beads in vivo. Indeed, TGFbeta was directly responsible not only for the enhanced macrophage phagocytosis but also altering the ratio of antigen-presenting cells to favour macrophages over DC.
24907113melanomaInhibit immunity (NK cell function); decrease the efficacy of immunotherapyPatient-derived moMDSCs inhibited NK-cell activity through the production of TGFβ. In vitro, binding of PGE2 to EP2 and EP4 receptors on monocytes activated the p38MAPK/ERK pathway and resulted in elevated secretion of TGFβ.
29632714breast carcinomaInhibit immunityMurine studies have suggested that countering immune suppressive effects of TGFβ may be sufficient to inhibit tumor growth.
27913437Breast Carcinoma; Lung Carcinoma; Colon CarcinomaInhibit immunity (T cell function)GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). We report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. In genetic studies in normal mammary gland epithelial and carcinoma cells, GARP expression increased TGFβ bioactivity and promoted malignant transformation in immunodeficient mice.
27756784NeuroblastomaInhibit immunity (NK cell function)The impact of galunisertib on TGFβ1-induced inhibition of aNK cytotoxicity and ADCC in vitro and on anti-neuroblastoma activity in NOD-scid gamma (NSG) mice was determined. Neuroblastomas express TGFB1 and TGFBR1 mRNA. Galunisertib suppressed SMAD activation in neuroblastoma cells induced by exogenous TGFβ1 or by patient blood and bone marrow plasma, and suppressed SMAD2 phosphorylation in human neuroblastoma cells growing in NSG mice.
23955389Prostate CarcinomaInhibit immunity (T cell function)Blockade of TGF-β signaling greatly enhances the efficacy of TCR gene therapy of cancer. Treatment of mice with advanced prostate cancer with T cells genetically engineered to express a tumor-reactive TCR and a dominant-negative TGF-β receptor II induces complete and sustained tumor regression, enhances survival, and leads to restored differentiation of prostate epithelium.
23904171MelanomaInhibit immunity (T cell function)Blockage of endogenous TGF-β with either a TGF-β-blocking Ab or a small molecule inhibitor of TGF-βRI enhances the generation of CD62L(high)/CD44(high) central memory CD8(+) T cells accompanied with a robust recall response.
21515097Colorectal CancinomaInhibit immunityIn addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population.
20150362GlioblastomaInhibit immunity (T/NK cell function)TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients. Despite the presence of soluble NKG2D ligands in the sera of glioblastoma patients, NKG2D downregulation was primarily caused by tumor-derived tumor growth factor-beta, suggesting that blocking of this cytokine may have therapeutic benefit.
20145137Breast CarcinomaInhibit immunityTo evaluate the potential role of tumor-derived, antiestrogen-induced TGFbeta as an immune suppressor, we established in vitro mixed lymphocyte tumor reactions (MLTR) using MCF-7 cells and peripheral blood mononuclear cells (PBMC), as well as tumor tissue and autologous tumor infiltrating lymphocytes (TIL) obtained from primary breast cancer biopsies.
20144842Ovarian CancinomaInhibit immunityBesides the immune-activating tumor infiltrating lymphocytes (TILs), immune-suppressive regulatory T-cells (Tregs), tolerance-inducing plasmacytoid dendritic cells (pDCs), B7-H4+ macrophages, immune-suppressive cytokines such as IL10 and TGF-beta are also found in the tumor environment.
20028741Renal Cell CarcinomaInhibit immunity (T cell function); resistant to immunotherapyTransforming growth factor-beta (TGF-beta) is a potent immunosuppressor that has been associated with tumor evasion from the host immune surveillance and, thus, tumor progression. Adoptive transfer of autologous TGF-beta-insensitive CD8(+) T cells into tumor-bearing Hu-PBMC-SCID mice induced robust tumor-specific CTL responses in vitro, were associated with tumor apoptosis, suppressed lung metastasis, and prolonged survival times in vivo.
29301578B16 Malignant MelanomaInhibit immunity (T cell function)The percentage of CD4+CD25+FoxP3+ Tregs and Gr1+CD11b+MDSCs were significantly increased in tumor microenvironment, and all these were attributed to the upregulation of TGF-β1.
18676771Breast CarcinomaInhibit immunityOverexpression of transforming growth factor (TGF)-beta has been implicated in promoting immune suppression, tumor angiogenesis, tumor cell migration, and invasion in many cancers, including carcinoma of the breast.
18559587Head and Neck Squamous Cell CarcinomaInhibit immunity (T cell function)Tr1 cells suppressed proliferation of autologous responders via IL-10 and TGF-beta1 secretion. In HNSCC, Tr1 cell generation is promoted at the tumor site. Tr1 cells use TGF-beta and IL-10 to mediate suppression.
18483277Colon Cacinoma; Breast CarcinomaInhibit immunityTransforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Overexpression of the immunosuppressive cytokine transforming growth factor beta (TGF-beta) is one strategy that tumors have developed to evade effective immunesurveillance. Thus, in addition to suppressing immune surveillance, tumor-induced TGF-beta may actively subvert the CD8+ arm of the immune system into directly promoting tumor growth by an IL-17-dependent mechanism.
18483268Breast CarcinomaInhibit immunity (T cell function); immunotherapy targetWe showed that efficacy of the anti-TGF-beta antibody 1D11 in suppressing metastasis was dependent on a synergistic combination of effects on both the tumor parenchyma and microenvironment. The main outcome was a highly significant enhancement of the CD8+ T-cell-mediated antitumor immune response, but effects on the innate immune response and on angiogenesis also contributed to efficacy.
29129643Non-Small Cell Lung CarcinomaInhibit immunityAberrant upregulation of TGFβ expression in the tumor microenvironment has also been implicated in promoting NSCLC progression and metastasis, as well as driving the development of resistance to cytotoxic, targeted, and immunomodulatory therapeutic interventions.
29721396Breast Carcinoma; Colon CarcinomaInhibit immunity; Immunotherapy targetSecretion of TGFβ and upregulation of immune checkpoint programmed cell death ligand-1 (PD-L1) are two main contributors to immune evasion and tumor progression. Here, we examined the efficacy of a first-in-class bifunctional checkpoint inhibitor, the fusion protein M7824, comprising the extracellular domain of human TGFβRII (TGFβ Trap) linked to the C-terminus of human anti-PD-L1 heavy chain (αPD-L1). We demonstrate that M7824 reduces plasma TGFβ1, binds to PD-L1 in the tumor, and decreases TGFβ-induced signaling in the tumor microenvironment in mice. These findings demonstrate the value of using M7824 to simultaneously target TGFβ and PD-L1/PD-1 immunosuppressive pathways to promote anti-tumor responses and efficacy.
29721376Non-Small Cell Lung CarcinomaInhibit immunityWe also demonstrated that the expression of PD-L1 required both TNFα and TGFβ1. Indeed, TGFβ1 decreased DNMT1 content and that resulted in PD-L1 promoter demethylation whereas TNFα induced the NF-κB pathway that promoted expression of demethylated PD-L1 promoter.
17644739Hodgkin LymphomaInhibit immunityRNA fingerprints provide direct evidence for the inhibitory role of TGFbeta and PD-1 on CD4+ T cells in Hodgkin lymphoma. Applying these specific fingerprints, we directly demonstrate that CD4+ T cells in HL--but not in follicular lymphoma (FL)--are under the inhibitory influence of both TGFbeta and PD-1 in vivo.
17565341Cutaneous MelanomaInhibit immunityOur results indicate that tolerogenic DCs and suppressor T lymphocytes are present in melanoma at all stages of disease progression. In primary melanoma, TGFbeta2 is likely to render peripheral DCs tolerogenic, while in lymph nodes IDO and TGFbeta1 may have a major effect.
16286245ThymomaInhibit immunity (T cell function)We demonstrate that TGF-beta acts on cytotoxic T lymphocytes (CTLs) to specifically inhibit the expression of five cytolytic gene products-namely, perforin, granzyme A, granzyme B, Fas ligand, and interferon gamma-which are collectively responsible for CTL-mediated tumor cytotoxicity. Repression of granzyme B and interferon-gamma involves binding of TGF-beta-activated Smad and ATF1 transcription factors to their promoter regions, indicating direct and selective regulation by the TGF-beta/Smad pathway.
16210663Malignant Head and Neck NeoplasmInhibit immunity (T cell function)Inhibition of NK cell activity through TGF-beta 1 by down-regulation of NKG2D in a murine model of head and neck cancer. Incubation of NK cells with tumor homogenate or cultured supernatant of SCC VII/SF cells reduced the expression of NKG2D and CD16. This inhibition appeared to be mediated by TGF-beta1. SCC VII/SF tumors in the oral cavity of the mice secrete high quantities of TGF-beta1, which reduce the expression of NK cell receptor NKG2D as well as CD16 and inhibits biological functions of NK cells.
25238097ovarian carcinomaInhibit immunity (T cell function)Mechanistically, Foxp1 interacted with the transcription factors Smad2 and Smad3 in preactivated CD8(+) T cells in response to microenvironmental transforming growth factor-beta (TGF-beta), and was essential for its suppressive activity. Therefore, Smad2 and Smad3-mediated c-Myc repression requires Foxp1 expression in T cells. Furthermore, Foxp1 directly mediated TGF-beta-induced c-Jun transcriptional repression, which abrogated T cell activity.
25205101melanomaInhibit immunityHowever, current protocols for ex vivo programming of Th17 cells, which include TGFbeta exposure, increase the expression of CD39 and CD73, two cell surface ATP ectonucleotidases that reduce T-cell effector functions and promote immunosuppression
25082897Childhood Brain GerminomaInhibit immunityIn this report, we show that blockade of T-cell TGF-β signaling directs expansion and activation of CTLs against MB. Specifically, blockade of this signaling pathway during MB malignancy promotes memory T-cell formation, conferring antitumor immunity
23262246Hepatocellular CarcinomaInhibit immunityThe functional impairment of HCC-infiltrating γδ T cells, partially mediated by regulatory T cells in a TGFβ- and IL-10-dependent manner.
21841316Breast CarcinomaInhibit immunityImportantly, Ti-NK cells had more pronounced impairment of their cytotoxic potential than p-NK cells. We also identified several stroma-derived factors, including TGF-beta1, involved in tumor-induced reduction of normal NK cell function.
21784871Breast CarcinomaInhibit immunityFurthermore, we showed that treatment with these NPs resulted in priming of the immune TME, characterized by increased IFN-gamma, p-STAT-1, GM-CSF, IL-2, IL-15, and IL-12b and reduced TGF-beta, IL-6, and IL-10 protein expression. In addition, we found significantly increased tumor infiltration by activated CD8(+) T cells, M1 macrophages, and dendritic cells.
16982774MelanomaInhibit immunityHere, we report the first evidence that tumor-released microvesicles alter myeloid cell function by impairing monocyte differentiation into dendritic cells and promoting the generation of a myeloid immunosuppressive cell subset. These phenotypic changes were paralleled by a significant release of different cytokines, including IL-6, tumor necrosis factor-alpha, and transforming growth factor-beta (TGF-beta), and a dose-dependent suppressive activity on activated T-cell-proliferation and cytolytic functions, which could be reversed by anti-TGF-beta-neutralizing antibodies.
16891318GlioblastomaInhibit immunityWe further delineate two independent mechanisms that can explain these expression patterns: (i) transforming growth factor-beta (TGF-beta) is upregulated during malignant progression and selectively downregulates MICA, ULBP2 and ULBP4 expression, while MICB, ULBP1 and ULBP3 are unaffected. (ii) Cleavage of MICA and ULBP2 is reduced by inhibition of metalloproteinases (MP), whereas no changes in the expression levels of other NKG2DL were detected. Consequently, NKG2DL-dependent NK cell-mediated lysis is enhanced by depletion of TGF-beta or inhibition of MP.
16891318GlioblastomaInhibit immunityWe further delineate two independent mechanisms that can explain these expression patterns: (i) transforming growth factor-beta (TGF-beta) is upregulated during malignant progression and selectively downregulates MICA, ULBP2 and ULBP4 expression, while MICB, ULBP1 and ULBP3 are unaffected. (ii) Cleavage of MICA and ULBP2 is reduced by inhibition of metalloproteinases (MP), whereas no changes in the expression levels of other NKG2DL were detected. Consequently, NKG2DL-dependent NK cell-mediated lysis is enhanced by depletion of TGF-beta or inhibition of MP.
16818744colon carcinomaInhibit immunityThese findings suggest that tumor growth facilitates the induction or recruitment of CD4+ regulatory T cells that secrete IL-10 and TGF-beta and suppress effector CD8+ T cell responses. However, CD8+ T regulatory cells expressing IL-10 and TGF-beta are also recruited or activated by the immunosuppressive environment of the lung, where they may suppress the induction of antitumor immunity.
Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of TGFB1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of TGFB1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.4240.288
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.8970.73
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0680.969
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.3020.444
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.3330.884
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2610.928
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2190.678
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2020.891
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2350.886
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9560.619
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.2030.676
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4822.57e-05
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TGFB1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TGFB1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TGFB1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TGFB1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TGFB1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TGFB1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TGFB1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTGFB1
Nametransforming growth factor, beta 1
Aliases TGFbeta; Camurati-Engelmann disease; prepro-transforming growth factor beta-1; TGFB; DPD1; TGF-beta-1; laten ......
Chromosomal Location19q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TGFB1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting TGFB1.
ID Name Drug Type Targets #Targets
DB00070HyaluronidaseBiotechTGFB11
DB06205Hyaluronidase (Human Recombinant)BiotechTGFB11