TISIDB

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
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 [ TOP ]
Subcellular Location	Cell membrane; Single-pass type I membrane protein.
Domain	PF00047 Immunoglobulin domain PF07714 Protein tyrosine kinase
Function	Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor.

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0001894 tissue homeostasis GO:0002521 leukocyte differentiation GO:0002573 myeloid leukocyte differentiation GO:0006644 phospholipid metabolic process GO:0006650 glycerophospholipid metabolic process GO:0007259 JAK-STAT cascade GO:0007260 tyrosine phosphorylation of STAT protein GO:0007409 axonogenesis GO:0007411 axon guidance GO:0008360 regulation of cell shape GO:0009306 protein secretion GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0021537 telencephalon development GO:0021772 olfactory bulb development GO:0021872 forebrain generation of neurons GO:0021879 forebrain neuron differentiation GO:0021953 central nervous system neuron differentiation GO:0021988 olfactory lobe development GO:0022604 regulation of cell morphogenesis GO:0022612 gland morphogenesis GO:0030099 myeloid cell differentiation GO:0030224 monocyte differentiation GO:0030225 macrophage differentiation GO:0030316 osteoclast differentiation GO:0030335 positive regulation of cell migration GO:0030879 mammary gland development GO:0030900 forebrain development GO:0031529 ruffle organization GO:0031532 actin cytoskeleton reorganization GO:0032602 chemokine production GO:0032642 regulation of chemokine production GO:0032722 positive regulation of chemokine production GO:0032844 regulation of homeostatic process GO:0032956 regulation of actin cytoskeleton organization GO:0032970 regulation of actin filament-based process GO:0033674 positive regulation of kinase activity GO:0034103 regulation of tissue remodeling GO:0034330 cell junction organization GO:0034331 cell junction maintenance GO:0035239 tube morphogenesis GO:0036005 response to macrophage colony-stimulating factor GO:0036006 cellular response to macrophage colony-stimulating factor stimulus GO:0038145 macrophage colony-stimulating factor signaling pathway GO:0040017 positive regulation of locomotion GO:0042503 tyrosine phosphorylation of Stat3 protein GO:0042509 regulation of tyrosine phosphorylation of STAT protein GO:0042516 regulation of tyrosine phosphorylation of Stat3 protein GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein GO:0043410 positive regulation of MAPK cascade GO:0043954 cellular component maintenance GO:0045124 regulation of bone resorption GO:0045216 cell-cell junction organization GO:0045217 cell-cell junction maintenance GO:0045453 bone resorption GO:0045860 positive regulation of protein kinase activity GO:0046425 regulation of JAK-STAT cascade GO:0046427 positive regulation of JAK-STAT cascade GO:0046486 glycerolipid metabolic process GO:0046488 phosphatidylinositol metabolic process GO:0046777 protein autophosphorylation GO:0046849 bone remodeling GO:0046850 regulation of bone remodeling GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0048667 cell morphogenesis involved in neuron differentiation GO:0048732 gland development GO:0048771 tissue remodeling GO:0048871 multicellular organismal homeostasis GO:0050663 cytokine secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050715 positive regulation of cytokine secretion GO:0050730 regulation of peptidyl-tyrosine phosphorylation GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0051047 positive regulation of secretion GO:0051222 positive regulation of protein transport GO:0051272 positive regulation of cellular component movement GO:0051493 regulation of cytoskeleton organization GO:0060249 anatomical structure homeostasis GO:0060443 mammary gland morphogenesis GO:0060562 epithelial tube morphogenesis GO:0060603 mammary gland duct morphogenesis GO:0061097 regulation of protein tyrosine kinase activity GO:0061098 positive regulation of protein tyrosine kinase activity GO:0061180 mammary gland epithelium development GO:0061564 axon development GO:0070371 ERK1 and ERK2 cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0090195 chemokine secretion GO:0090196 regulation of chemokine secretion GO:0090197 positive regulation of chemokine secretion GO:0097485 neuron projection guidance GO:0097696 STAT cascade GO:1903131 mononuclear cell differentiation GO:1903532 positive regulation of secretion by cell GO:1904892 regulation of STAT cascade GO:1904894 positive regulation of STAT cascade GO:1904951 positive regulation of establishment of protein localization GO:2000147 positive regulation of cell motility GO:2000249 regulation of actin cytoskeleton reorganization
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0004714 transmembrane receptor protein tyrosine kinase activity GO:0005011 macrophage colony-stimulating factor receptor activity GO:0019199 transmembrane receptor protein kinase activity GO:0019902 phosphatase binding GO:0019903 protein phosphatase binding GO:0019955 cytokine binding
Cellular Component	GO:1990682 CSF1-CSF1R complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04014 Ras signaling pathway hsa04015 Rap1 signaling pathway hsa04060 Cytokine-cytokine receptor interaction hsa04144 Endocytosis hsa04151 PI3K-Akt signaling pathway hsa04380 Osteoclast differentiation hsa04640 Hematopoietic cell lineage
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-449147: Signaling by Interleukins

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CSF1R 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

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Literatures describing the relation between CSF1R and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26957560	Neuroblastoma	Inhibit immunity	Our results demonstrate the essential role of CSF-1R signaling during the induction of suppressive myeloid cells and emphasize its clinical potential as an immunotherapy for human cancers.
28536100	Mesothelioma	Inhibit immunity	We show that M-CSFR inhibition using the CSF-1R kinase inhibitor PLX3397 (pexidartinib) effectively reduced numbers of tumor-associated macrophages (TAMs) . TAM depletion could potentially reactivate antitumor immunity.
23418320	Prostate Carcinoma	Inhibit immunity (infiltration)	Enhanced macrophage migration induced by conditioned media from irradiated tumor cells was completely blocked by a selective inhibitor of CSF1R. These findings were confirmed in patients with prostate cancer, where serum levels of CSF1 increased after radiotherapy.
29632196	Squamous Cell Carcinoma	Inhibit immunity (infiltration)	Our results reveal that a CSF-1R blockade enhances CD8 T cell migration and infiltration into tumor islets.
29436395	Melanoma	Inhibit immunity; immunotherapy target	We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth.
24247719	Melanoma	Inhibit immunity; Resistant to immunotherapy	Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy. In mice receiving the combined treatment, a dramatic reduction of TIMs and a skewing of MHCII(low) to MHCII(hi) macrophages were observed. Furthermore, mice receiving the combined treatment exhibited an increase in tumor-infiltrating lymphocytes (TIL) and T cells, as revealed by real-time imaging in vivo. In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.
25082815	pancreatic carcinoma	Inhibit immunity	CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models
23221383	pancreatic carcinoma	Inhibit immunity	Targeting CCR2 or CSF1R improves chemotherapeutic efficacy, inhibits metastasis, and increases antitumor T-cell responses.

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
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

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Statistical results of CSF1R in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
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

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Points in the above scatter plot represent the expression difference of CSF1R in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.028	0.95
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.196	0.923
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.094	0.95
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.328	0.487
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.189	0.932
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.987	0.743
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.275	0.576
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.663	0.697
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.232	0.908
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.151	0.537
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.395	0.622
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.311	0.0708

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CSF1R in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	25	0	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	2.7	1	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	11.8	-7	0.577
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	33.3	-33.3	0.165
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	7.4	-4.8	0.565
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CSF1R. 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 [ TOP ]

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CSF1R. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CSF1R. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CSF1R. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CSF1R expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CSF1R and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CSF1R
Name	colony stimulating factor 1 receptor
Aliases	C-FMS; CSFR; CD115; FMS; McDonough feline sarcoma viral (v-fms) oncogene homolog; CSF-1R; FIM2; HDLS; M-CSF- ......
Chromosomal Location	5q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CSF1R collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CSF1R.

ID	Name	Drug Type	Targets	#Targets
DB00619	Imatinib	Small Molecule	ABL1, CSF1R, DDR1, KIT, NTRK1, PDGFRA, PDGFRB	7
DB01268	Sunitinib	Small Molecule	CSF1R, FLT1, FLT3, FLT4, KDR, KIT, PDGFRA, PDGFRB	8
DB06080	ABT-869	Small Molecule	CSF1R, FLT1, FLT3, FLT4, KDR, KIT	6
DB07167	5-CYANO-FURAN-2-CARBOXYLIC ACID [5-HYDROXYMETHYL-2-(4-METHYL-PIPERIDIN-1-YL)-PHENYL]-AMIDE	Small Molecule	CSF1R	1
DB07202	6-CHLORO-3-(3-METHYLISOXAZOL-5-YL)-4-PHENYLQUINOLIN-2(1H)-ONE	Small Molecule	CSF1R	1

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