Browse FOXP3

Summary
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
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 Nucleus Cytoplasm Note=Predominantly expressed in the cytoplasm in activated conventional T-cells whereas predominantly expressed in the nucleus in regulatory T-cells (Treg). The 41 kDa form derived by proteolytic processing is found exclusively in the chromatin fraction of activated Treg cells (By similarity).
Domain PF00250 Forkhead domain
PF16159 FOXP coiled-coil domain
Function

Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells. Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases. The suppressive activity of Treg involves the coordinate activation of many genes, including CTLA4 and TNFRSF18 by FOXP3 along with repression of genes encoding cytokines such as interleukin-2 (IL2) and interferon-gamma (IFNG). Inhibits cytokine production and T-cell effector function by repressing the activity of two key transcription factors, RELA and NFATC2 (PubMed:15790681). Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7 (PubMed:17360565). Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1 (PubMed:17377532). Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development (PubMed:18368049). Inhibits the transcriptional activator activity of RORA (PubMed:18354202). Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4 (By similarity).

> Gene Ontology
 
Biological Process GO:0000018 regulation of DNA recombination
GO:0001776 leukocyte homeostasis
GO:0001782 B cell homeostasis
GO:0001818 negative regulation of cytokine production
GO:0001819 positive regulation of cytokine production
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:0002249 lymphocyte anergy
GO:0002250 adaptive immune response
GO:0002260 lymphocyte homeostasis
GO:0002262 myeloid cell homeostasis
GO:0002263 cell activation involved in immune response
GO:0002285 lymphocyte activation involved in immune response
GO:0002286 T cell activation involved in immune response
GO:0002287 alpha-beta T cell activation involved in immune response
GO:0002292 T cell differentiation involved in immune response
GO:0002293 alpha-beta T cell differentiation involved in immune response
GO:0002294 CD4-positive, alpha-beta T cell differentiation involved in immune response
GO:0002312 B cell activation involved in immune response
GO:0002360 T cell lineage commitment
GO:0002361 CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation
GO:0002362 CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment
GO:0002363 alpha-beta T cell lineage commitment
GO:0002366 leukocyte activation involved in immune response
GO:0002367 cytokine production involved in immune response
GO:0002369 T cell cytokine production
GO:0002377 immunoglobulin production
GO:0002381 immunoglobulin production involved in immunoglobulin mediated immune response
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002456 T cell mediated immunity
GO:0002458 peripheral T cell tolerance induction
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002461 tolerance induction dependent upon immune response
GO:0002465 peripheral tolerance induction
GO:0002507 tolerance induction
GO:0002513 tolerance induction to self antigen
GO:0002517 T cell tolerance induction
GO:0002521 leukocyte differentiation
GO:0002544 chronic inflammatory response
GO:0002562 somatic diversification of immune receptors via germline recombination within a single locus
GO:0002637 regulation of immunoglobulin production
GO:0002638 negative regulation of immunoglobulin production
GO:0002643 regulation of tolerance induction
GO:0002645 positive regulation of tolerance induction
GO:0002652 regulation of tolerance induction dependent upon immune response
GO:0002654 positive regulation of tolerance induction dependent upon immune response
GO:0002658 regulation of peripheral tolerance induction
GO:0002660 positive regulation of peripheral tolerance induction
GO:0002664 regulation of T cell tolerance induction
GO:0002666 positive regulation of T cell tolerance induction
GO:0002667 regulation of T cell anergy
GO:0002669 positive regulation of T cell anergy
GO:0002676 regulation of chronic inflammatory response
GO:0002677 negative regulation of chronic inflammatory response
GO:0002683 negative regulation of immune system process
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:0002703 regulation of leukocyte mediated immunity
GO:0002704 negative regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002707 negative regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002709 regulation of T cell mediated immunity
GO:0002710 negative regulation of T cell mediated immunity
GO:0002711 positive regulation of T cell mediated immunity
GO:0002712 regulation of B cell mediated immunity
GO:0002713 negative 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:0002724 regulation of T cell cytokine production
GO:0002725 negative regulation of T cell cytokine production
GO:0002757 immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0002819 regulation of adaptive immune response
GO:0002820 negative 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:0002823 negative 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:0002849 regulation of peripheral T cell tolerance induction
GO:0002851 positive regulation of peripheral T cell tolerance induction
GO:0002870 T cell anergy
GO:0002889 regulation of immunoglobulin mediated immune response
GO:0002890 negative regulation of immunoglobulin mediated immune response
GO:0002911 regulation of lymphocyte anergy
GO:0002913 positive regulation of lymphocyte anergy
GO:0006310 DNA recombination
GO:0006338 chromatin remodeling
GO:0006473 protein acetylation
GO:0006475 internal protein amino acid acetylation
GO:0006476 protein deacetylation
GO:0007159 leukocyte cell-cell adhesion
GO:0007162 negative regulation of cell adhesion
GO:0009306 protein secretion
GO:0009615 response to virus
GO:0016064 immunoglobulin mediated immune response
GO:0016444 somatic cell DNA recombination
GO:0016445 somatic diversification of immunoglobulins
GO:0016447 somatic recombination of immunoglobulin gene segments
GO:0016570 histone modification
GO:0016573 histone acetylation
GO:0016575 histone deacetylation
GO:0018205 peptidyl-lysine modification
GO:0018393 internal peptidyl-lysine acetylation
GO:0018394 peptidyl-lysine acetylation
GO:0019724 B cell mediated immunity
GO:0022407 regulation of cell-cell adhesion
GO:0022408 negative regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030098 lymphocyte differentiation
GO:0030217 T cell differentiation
GO:0031056 regulation of histone modification
GO:0031057 negative regulation of histone modification
GO:0031058 positive regulation of histone modification
GO:0031063 regulation of histone deacetylation
GO:0031064 negative regulation of histone deacetylation
GO:0031348 negative regulation of defense response
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032102 negative regulation of response to external stimulus
GO:0032609 interferon-gamma production
GO:0032613 interleukin-10 production
GO:0032620 interleukin-17 production
GO:0032623 interleukin-2 production
GO:0032633 interleukin-4 production
GO:0032634 interleukin-5 production
GO:0032635 interleukin-6 production
GO:0032640 tumor necrosis factor production
GO:0032649 regulation of interferon-gamma production
GO:0032653 regulation of interleukin-10 production
GO:0032660 regulation of interleukin-17 production
GO:0032663 regulation of interleukin-2 production
GO:0032673 regulation of interleukin-4 production
GO:0032674 regulation of interleukin-5 production
GO:0032675 regulation of interleukin-6 production
GO:0032680 regulation of tumor necrosis factor production
GO:0032689 negative regulation of interferon-gamma production
GO:0032693 negative regulation of interleukin-10 production
GO:0032700 negative regulation of interleukin-17 production
GO:0032703 negative regulation of interleukin-2 production
GO:0032713 negative regulation of interleukin-4 production
GO:0032714 negative regulation of interleukin-5 production
GO:0032715 negative regulation of interleukin-6 production
GO:0032720 negative regulation of tumor necrosis factor production
GO:0032753 positive regulation of interleukin-4 production
GO:0032792 negative regulation of CREB transcription factor activity
GO:0032829 regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation
GO:0032831 positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation
GO:0032905 transforming growth factor beta1 production
GO:0032908 regulation of transforming growth factor beta1 production
GO:0032914 positive regulation of transforming growth factor beta1 production
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032945 negative regulation of mononuclear cell proliferation
GO:0032946 positive regulation of mononuclear cell proliferation
GO:0033077 T cell differentiation in thymus
GO:0033079 immature T cell proliferation
GO:0033080 immature T cell proliferation in thymus
GO:0033081 regulation of T cell differentiation in thymus
GO:0033083 regulation of immature T cell proliferation
GO:0033084 regulation of immature T cell proliferation in thymus
GO:0033089 positive regulation of T cell differentiation in thymus
GO:0033091 positive regulation of immature T cell proliferation
GO:0033092 positive regulation of immature T cell proliferation in thymus
GO:0035065 regulation of histone acetylation
GO:0035066 positive regulation of histone acetylation
GO:0035067 negative regulation of histone acetylation
GO:0035601 protein deacylation
GO:0035710 CD4-positive, alpha-beta T cell activation
GO:0042035 regulation of cytokine biosynthetic process
GO:0042036 negative regulation of cytokine biosynthetic process
GO:0042089 cytokine biosynthetic process
GO:0042093 T-helper cell differentiation
GO:0042094 interleukin-2 biosynthetic process
GO:0042095 interferon-gamma biosynthetic process
GO:0042098 T cell proliferation
GO:0042102 positive regulation of T cell proliferation
GO:0042107 cytokine metabolic process
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:0043029 T cell homeostasis
GO:0043367 CD4-positive, alpha-beta T cell differentiation
GO:0043368 positive T cell selection
GO:0043369 CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
GO:0043370 regulation of CD4-positive, alpha-beta T cell differentiation
GO:0043371 negative regulation of CD4-positive, alpha-beta T cell differentiation
GO:0043372 positive regulation of CD4-positive, alpha-beta T cell differentiation
GO:0043373 CD4-positive, alpha-beta T cell lineage commitment
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043543 protein acylation
GO:0045058 T cell selection
GO:0045066 regulatory T cell differentiation
GO:0045072 regulation of interferon-gamma biosynthetic process
GO:0045076 regulation of interleukin-2 biosynthetic process
GO:0045077 negative regulation of interferon-gamma biosynthetic process
GO:0045085 negative regulation of interleukin-2 biosynthetic process
GO:0045165 cell fate commitment
GO:0045190 isotype switching
GO:0045191 regulation of isotype switching
GO:0045580 regulation of T cell differentiation
GO:0045581 negative 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:0045619 regulation of lymphocyte differentiation
GO:0045620 negative regulation of lymphocyte differentiation
GO:0045621 positive regulation of lymphocyte differentiation
GO:0045622 regulation of T-helper cell differentiation
GO:0045623 negative regulation of T-helper cell differentiation
GO:0045785 positive regulation of cell adhesion
GO:0045829 negative regulation of isotype switching
GO:0045910 negative regulation of DNA recombination
GO:0046006 regulation of activated T cell proliferation
GO:0046007 negative regulation of activated T cell proliferation
GO:0046631 alpha-beta T cell activation
GO:0046632 alpha-beta T cell differentiation
GO:0046634 regulation of alpha-beta T cell activation
GO:0046635 positive regulation of alpha-beta T cell activation
GO:0046636 negative regulation of alpha-beta T cell activation
GO:0046637 regulation of alpha-beta T cell differentiation
GO:0046638 positive regulation of alpha-beta T cell differentiation
GO:0046639 negative regulation of alpha-beta T cell differentiation
GO:0046651 lymphocyte proliferation
GO:0048289 isotype switching to IgE isotypes
GO:0048291 isotype switching to IgG isotypes
GO:0048293 regulation of isotype switching to IgE isotypes
GO:0048294 negative regulation of isotype switching to IgE isotypes
GO:0048302 regulation of isotype switching to IgG isotypes
GO:0048872 homeostasis of number of cells
GO:0050663 cytokine secretion
GO:0050670 regulation of lymphocyte proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050672 negative regulation of lymphocyte proliferation
GO:0050707 regulation of cytokine secretion
GO:0050708 regulation of protein secretion
GO:0050709 negative regulation of protein secretion
GO:0050710 negative regulation of cytokine secretion
GO:0050727 regulation of inflammatory response
GO:0050728 negative regulation of inflammatory response
GO:0050777 negative regulation of immune response
GO:0050798 activated T cell proliferation
GO:0050851 antigen receptor-mediated signaling pathway
GO:0050852 T cell receptor signaling pathway
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:0050869 negative regulation of B cell activation
GO:0050870 positive regulation of T cell activation
GO:0051048 negative 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:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051224 negative regulation of protein transport
GO:0051249 regulation of lymphocyte activation
GO:0051250 negative regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070664 negative regulation of leukocyte proliferation
GO:0070665 positive regulation of leukocyte proliferation
GO:0071593 lymphocyte aggregation
GO:0071594 thymocyte aggregation
GO:0071604 transforming growth factor beta production
GO:0071634 regulation of transforming growth factor beta production
GO:0071636 positive regulation of transforming growth factor beta production
GO:0071706 tumor necrosis factor superfamily cytokine production
GO:0072538 T-helper 17 type immune response
GO:0072539 T-helper 17 cell differentiation
GO:0090311 regulation of protein deacetylation
GO:0098732 macromolecule deacylation
GO:1901983 regulation of protein acetylation
GO:1901984 negative regulation of protein acetylation
GO:1901985 positive regulation of protein acetylation
GO:1902105 regulation of leukocyte differentiation
GO:1902106 negative regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1902275 regulation of chromatin organization
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:1903531 negative regulation of secretion by cell
GO:1903555 regulation of tumor necrosis factor superfamily cytokine production
GO:1903556 negative regulation of tumor necrosis factor superfamily cytokine production
GO:1903706 regulation of hemopoiesis
GO:1903707 negative regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1904950 negative regulation of establishment of protein localization
GO:1905268 negative regulation of chromatin organization
GO:1905269 positive regulation of chromatin organization
GO:2000316 regulation of T-helper 17 type immune response
GO:2000317 negative regulation of T-helper 17 type immune response
GO:2000319 regulation of T-helper 17 cell differentiation
GO:2000320 negative regulation of T-helper 17 cell differentiation
GO:2000398 regulation of thymocyte aggregation
GO:2000400 positive regulation of thymocyte aggregation
GO:2000514 regulation of CD4-positive, alpha-beta T cell activation
GO:2000515 negative regulation of CD4-positive, alpha-beta T cell activation
GO:2000516 positive regulation of CD4-positive, alpha-beta T cell activation
GO:2000756 regulation of peptidyl-lysine acetylation
GO:2000757 negative regulation of peptidyl-lysine acetylation
GO:2000758 positive regulation of peptidyl-lysine acetylation
Molecular Function GO:0001047 core promoter binding
GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0003714 transcription corepressor activity
GO:0008134 transcription factor binding
GO:0035035 histone acetyltransferase binding
GO:0042826 histone deacetylase binding
GO:0051059 NF-kappaB binding
GO:0051525 NFAT protein binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG -
Reactome -
Summary
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between FOXP3 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 FOXP3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28249894Plasma Cell MyelomaInhibit immunity (T cell function)We study CD38 levels in immunosuppressive CD4+CD25highFoxp3+regulatory T cells (Treg) and further define immunomodulating effects of a therapeutic CD38 mAb isatuximab/SAR650984 in multiple myeloma. Isatuximab reduces Foxp3 and IL10 in Tregs and restores proliferation and function of Tcons.
26324768Hepatocellular CarcinomaInhibit immunity (T cell function)FOXP3/NFAT interaction is required to repress expression of IL-2, upregulate expression of the Treg markers CTLA4 and CD25, and confer suppressor function to Tregs.
22569001Gastric CarcinomaInhibit immunity (T cell function)Our findings suggested that FoxP3 expression by tumour cells might have important roles in immune escape of gastric carcinoma, and be associated with the malignant potential of scirrhous gastric carcinoma. Indoleamine-2,3-dioxygenase and galectin-1, key effectors of Treg-mediated immunosuppression, were downregulated by FoxP3 knockdown.
18413832Breast carcinomaInhibit immunityThese findings indicate that pCR to neoadjuvant chemotherapy is associated with an immunologic profile combining the absence of immunosuppressive Foxp3 cells and the presence of a high number of CD8 T cells and cytotoxic cells.
23090488MelanomaInhibit immunityIn the B16F10 melanoma model, we show that single vaccination with irradiated, α-GalCer-loaded tumor cells resulted in suppression of established subcutaneous (s.c.) B16F10 tumor growth, which was mediated by NKT cell-dependent IFN-γ production and enhanced in the absence of IL-17?A. Selective depletion of Foxp3(+) Tregs in transgenic DEpletion of REGulatory T cells (DEREG) mice led to significant inhibition of B16F10 tumor growth and enhanced survival of mice receiving vaccination. Short-term elimination of Foxp3(+) Tregs (<7 days) was sufficient to boost vaccine-induced immunity.
19318244Prostate carcinomaInhibit immunityWe had previously documented that prostate cancer islets are surrounded by clustered accumulations of CD3+ lymphocytes, which lack perforin and interferon-gamma (IFNgamma) expression, thus are apparently quiescent. Here, we report that these clusters contain numerous CD25+ and FOXP3+ cells. These markers are associated with regulatory T cells, and their presence in lymphocyte clusters near prostate cancer regions indicates an environment with negative impact on immune response against cancer cells.
28470686Pancreatic Carcinoma; Ampulla of Vater CarcinomaInhibit immunity (T cell function)Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Expression of immune inhibitory molecules and TIL was examined by immunohistochemistry. We show that immune inhibitory molecules are prevalently expressed. Moreover, high tumor expression of PD-L1 (p?=?0.002), Gal-9 (p?=?0.003), HVEM (p?=?0.001), IDO (p?=?0.049), HLA-G (p?=?0.004) and high CD8/FoxP3 TIL ratio (p?=?0.006) were associated with improved cancer-specific survival.
23447383Chronic Lymphocytic LeukemiaInhibit immunity (T cell function)In our study, we characterized mRNA levels of VEGF receptors including NRP1 in a large cohort of CLL patients (n = 114), additionally we performed a detailed characterization of NRP1 expression on B cells, plasmacytoid dendritic cells (PDCs) and regulatory T cells (Tregs). The expression of NRP1 was significantly higher on leukemic lymphocytes compared to control B lymphocytes on mRNA and protein levels (22.72% vs. 0.2%, p = 0.0003, respectively), Tregs (42.6% vs. 16.05%, p = 0.0003) and PDCs (100% vs. 98% p < 0.0001). In functional studies, we found higher NRP1 expression on CLL cells after stimulation with VEGF. The correlation between expression of VEGF receptors: FLT1, NRP1 and FOXP3 expression (r(2) = 0.53, p < 0.0001 and r(2) = 0.49, p < 0.0001, respectively) was observed.
19549768Cervical CarcinomaInhibit immunity (T cell function)We used the HPV16 E6- and E7-expressing TC-1 mouse tumor model to study the effect of TAM on T-cell function in vitro, and depleted TAM, using clodronate-containing liposomes, to characterize its role in vivo. TAM displayed high basal Arginase I activity, producing interleukin-10 (IL-10); they were resistant to iNOSII activity induction, therefore reversion to M1 phenotype, when stimulated in vitro with lipopolysaccharide/IFNgamma, indicating an M2 phentoype. In cultures of isolated TAM, TAM induced regulatory phenotype, characterized by IL-10 and Foxp3 expression, and inhibited proliferation of CD8 lymphocytes.
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.
17804750Pancreatic Ductal AdenocarcinomaInhibit immunity (T cell function)Coculture of Foxp3-expressing tumor cells with naive T cells completely inhibited T-cell proliferation, but not activation, and this antiproliferative effect was partially abrogated following specific inhibition of Foxp3 expression.
29661773pancreatic ductal adenocarcinomaInhibit immunityThree PDAC subtypes were identified: the immune escape (54%), poor in T and B cells and enriched in FOXP3+ regulatory T cells (Treg), with high-grade budding, frequent CDKN2A, SMAD4, and PIK3CA mutations, and poor outcome; the immune rich (35%), rich in T and B cells and poorer in FOXP3+ Tregs, with infrequent budding, lower CDKN2A and PIK3CA mutation rate, and better outcome and a subpopulation with tertiary lymphoid tissue (TLT), mutations in DNA damage response genes (STK11 and ATM), and the best outcome; and the immune exhausted (11%), with immunogenic microenvironment and two subpopulations-one with PD-L1 expression and a high PIK3CA mutation rate and a microsatellite-unstable subpopulation with a high prevalence of JAK3 mutations.
29581358colorectal carcinomaInhibit immunityWith histopathological analysis, Foxp3+ Tregs were preferentially located in stroma.
27913437Breast CarcinomaInhibit immunity (T cell function)In breast carcinoma-bearing mice that were immunocompetent, GARP overexpression promoted Foxp3+ Treg activity, which in turn contributed to enhancing cancer progression and metastasis.
23986400MelanomaInhibit immunity (infiltration)In the current report, we show that it is the subset of T cell-inflamed tumors that showed high expression of three defined immunosuppressive mechanisms: indoleamine-2,3-dioxygenase (IDO), PD-L1/B7-H1, and FoxP3(+) regulatory T cells (T(regs)), suggesting that these inhibitory pathways might serve as negative feedback mechanisms that followed, rather than preceded, CD8(+) T cell infiltration.
20145137Breast CarcinomaInhibit immunity (T cell function)Furthermore, we documented induction of regulatory T cells in CD4(+) T cells, based on Foxp3 expression and T-cell activation in cocultures. In autologous MLTR, antiestrogen treatment gave rise to enhanced Foxp3 expression of TIL/PBMC and decreased the number of apoptotic tumor cells.
29361059Renal Cell CarcinomaInhibit immunityPD-1, PD-L2, CTLA4 and FOXP3, all of which are implicated in the evasion of an anti-tumor immune response, had a significantly higher expression for samples representing co-detection of productive TcR-α and -β recombination reads.
29307625Vulvar MelanomaPromote immunityIn conclusion, our study shows that, independent from tumor thickness, an increased density of peritumoral FoxP3+ lymphocytes may positively impact survival in a subset of vulvar melanomas.
29124314MelanomaPromote immunityIn conclusion, our results revealed that Foxp3 vaccine promotes an immune response against tumor by targeting both Treg and MDSC, which could be exploited as a potential immunotherapy approach.
18533240Endometrial AdenocarcinomaInhibit immunity (infiltration)CD4(+)CD25(+) regulatory T-cells (Tregs), that express the transcription factor FOXP3, suppress effector T-cell populations and can enable tumour cells to evade the host immune response. In tumors, 55/79 (69.6%) cases showed little FOXP3(+) lymphocytic infiltration (0-2 per x100 optical field).
16034085Lung CarcinomaInhibit immunity (T cell function)PGE2 exposure induced the T reg cell-specific transcription factor forkhead/winged helix transcription factor gene (FOXP3) in CD4+CD25- T cells and significantly up-regulated its expression in CD4+CD25+ T reg cells.
15958566Non-Small Cell Lung CarcinomaInhibit immunityTumor-derived COX-2/PGE2 induced expression of the Treg cell-specific transcription factor, Foxp3, and increased Treg cell activity.
27991933Pancreatic Ductal AdenocarcinomaInhibit immunityCancer-FOXP3 directly activated CCL5 to recruit FOXP3+Treg cells in pancreatic ductal adenocarcinoma. In addition, high cancer-FOXP3 expression was associated with increased tumor volumes and poor prognosis in PDAC especially combined with high levels of Treg cells.
24416730MelanomaInhibit immunityComplete Foxp3 loss in intra-tumor Treg correlates with a dramatic decrease in Helios expression and is associated with the upregulation of transcription factors T-Bet and Eomes. Changes in Helios correspond with a reduction in IL-10 and an increase in IFNγ expression in DTA-1-treated Treg.
22850422Ovarian CarcinomaInhibit immunityPlasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3(+) T-regulatory cells. Accordingly, ICOS(+) Foxp3(+) Treg cells were found to localize in close vicinity of tumor pDCs, and their number directly correlated with the numbers of pDCs in the tumors. Furthermore, pDCs and ICOS(+) Foxp3(+) Treg cells were found to be strong predictors for disease progression in patients with ovarian cancer, with ICOS(+) Treg cell subset being a stronger predictor than total Foxp3(+) Treg cells.
21670203MelanomaInhibit immunityFoxp3-positive macrophages display immunosuppressive properties and promote tumor growth. Analysis of CD11b(+)F4/80(+)Foxp3(+) macrophage function indicated that these cells inhibited the proliferation of T cells, whereas Foxp3(-) macrophages did not. Foxp3(-) macrophages acquired Foxp3 expression after activation, which conferred inhibitory properties that were indistinguishable from natural Foxp3(+) macrophages. Functional in vivo analyses indicated that CD11b(+)F4/80(+)Foxp3(+) macrophages are important in tumor promotion and the induction of T reg cell conversion.
20682706Colorectal CarcinomaInhibit immunityThe density of Foxp3(+) Tregs in TDLNs was dramatically higher than that in peripheral blood lymphocytes, but significantly lower than that in tumor-infiltrating lymphocytes. Importantly, the frequency of Foxp3(+) Tregs in TDLNs, rather than that in tumors and peripheral blood, was positively correlated with disease stage. Foxp3(+) Tregs in TDLNs are more correlated with disease progression and potentially influence CD8(+) T-cell functions.
20525891Adult T-Cell Leukemia/LymphomaInhibit immunityFinally, we show that FoxP3(+) cells inhibit the proliferation of ex vivo, autologous leukemic clones from patients with ATLL. We conclude that HTLV-1-induced CCL22 causes the high frequency of FoxP3(+) cells observed in HTLV-1 infection; these FoxP3(+) cells may both retard the progression of ATLL and HTLV-1-associated inflammatory diseases and contribute to the immune suppression seen in HTLV-1 infection, especially in ATLL.
20234320Non-Small Cell Lung CarcinomaInhibit immunityTumor-infiltrating Foxp3-positive lymphocytes were positively correlated with COX-2 expression. The RFS of patients with tumors containing >or=3 Foxp3-positive cells (Foxp3 expression group) was significantly worse than that of patients with tumors containing <3 Foxp3-positive cells.
18820666Breast CarcinomaInhibit immunityHigher average numbers of FoxP3-positive cells present significantly correlated with higher Nottingham grade status (P=0.000229). Higher average numbers of FoxP3-positive cells were also significantly associated with larger tumor size (>2.0 cm; P=0.012824) and trended toward an association with estrogen receptor negativity.
17565340FibrosarcomaInhibit immunityWe surmised that immune surveillance would be hampered by the inhibitory effect of naturally occurring FoxP3(+) regulatory T cells, a population of T cells shown to be present at an increased frequency in a variety of human tumours. These fibrosarcomas were strikingly infiltrated with FoxP3(+) regulatory T cells implying that these cells impinge upon immune-mediated rejection of the tumour. This was confirmed by partial ablation of FoxP3(+) regulatory T-cell activity, which resulted in a marked reduction in tumour incidence.
25225903colorectal carcinomaInhibit immunityMoreover, FOXP3 expression has also been seen in tumour cells, which may also provide tumours with direct immunosuppressive powers (Hinz et al, 2007; Ebert et al, 2008)
25187059breast carcinomaInhibit immunity (T cell function)Involution breast tissue also contained an elevated number of Foxp31 immune cells that costained for CD4, suggesting the presence of regulatory T cells (Fig. 6b and Supporting Information Fig. S7d).
25183499melanomaInhibit immunityIn the tumor microenvironment, BRAF inhibitor PLX4720 functioned by on-target mechanisms to selectively decrease both the proportions and absolute numbers of CD4(+)Foxp3(+) regulatory T cells (Treg) and CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSC), while preserving numbers of CD8(+) effector T cells
23378296Breast CarcinomaPromote immunityIn a related biochemical assay, the rs2294021C allele was found to significantly enhance transcription activity, leading to higher mRNA levels of FOXP3 compared with T allele. Moreover, the number of Tregs and its corresponding interleukin-10 (IL-10) secretion were elevated whereas the proliferation of antitumor T cells was decreased in the C-allele carriers.
23319800MelanomaInhibit immunityInterestingly, tumor growth in p53(null) mice was greatly accelerated, correlating with marked increases in CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSC), FoxP3(+) regulatory T cells, and a loss of effector function, compared with those in WT mice.
16885376Breast CarcinomaInhibit immunityRepeated administration of anti-CD25 antibodies extends tumor-free survival, reduces carcinoma multiplicity, and leads to the manifestation of a natural antibody and CTL-mediated reactivity against r-Erbb2. Loss of Foxp3(+) Treg cells during anti-CD25 treatment remarkably caused the disappearance of Gr1(+) immature myeloid cells, suggesting a cross-talk between these two inhibitory immune cell types. Treg cell expansion associated with r-Erbb2 overexpression may be seen as a physiologic response to dampen the immune reaction elicited by local anomalous overexpression of a self-antigen.
Summary
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
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 FOXP3 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
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
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 FOXP3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0090.981
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.0790.921
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0770.901
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.5930.253
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1370.927
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.1780.57
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.6260.196
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.6690.364
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.5570.48
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.6580.00549
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.4470.0894
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0750.688
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of FOXP3 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) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)2117011.8-11.80.193
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)1311018.2-18.20.199
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.17.71.41
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6116.7016.71
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 51208.3-8.31
Summary
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FOXP3. 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
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FOXP3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FOXP3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FOXP3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of FOXP3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between FOXP3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolFOXP3
Nameforkhead box P3
Aliases JM2; XPID; AIID; PIDX; DIETER; SCURFIN; IPEX; immune dysregulation, polyendocrinopathy, enteropathy, X-linke ......
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting FOXP3 collected from DrugBank database.
> Drugs from DrugBank database
 

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