TISIDB

Summary
Symbol	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
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	Isoform 1: Cell membrane Multi-pass membrane protein ; SUBCELLULAR LOCATION: Isoform 2: Cell membrane Multi-pass membrane protein
Domain	PF00001 7 transmembrane receptor (rhodopsin family)
Function	Isoform 1: Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling pathway (PubMed:12782716). Binds to CCL21. Probably promotes cell chemotaxis response. ; FUNCTION: Isoform 2: Receptor for the C-X-C chemokine CXCL4 and also mediates the inhibitory activities of CXCL9, CXCL10 and CXCL11 on the proliferation, survival and angiogenic activity of human microvascular endothelial cells (HMVEC) through a cAMP-mediated signaling pathway (PubMed:12782716). Does not promote cell chemotaxis respons. Interaction with CXCL4 or CXCL10 leads to activation of the p38MAPK pathway and contributes to inhibition of angiogenesis. Overexpression in renal cancer cells down-regulates expression of the anti-apoptotic protein HMOX1 and promotes apoptosis. ; FUNCTION: Isoform 3: Mediates the activity of CXCL11.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0002685 regulation of leukocyte migration GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0010818 T cell chemotaxis GO:0019722 calcium-mediated signaling GO:0019932 second-messenger-mediated signaling GO:0030595 leukocyte chemotaxis GO:0048247 lymphocyte chemotaxis GO:0048514 blood vessel morphogenesis GO:0050900 leukocyte migration GO:0051480 regulation of cytosolic calcium ion concentration GO:0055074 calcium ion homeostasis GO:0060326 cell chemotaxis GO:0070098 chemokine-mediated signaling pathway GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072676 lymphocyte migration GO:0072678 T cell migration
Molecular Function	GO:0001637 G-protein coupled chemoattractant receptor activity GO:0001653 peptide receptor activity GO:0004896 cytokine receptor activity GO:0004950 chemokine receptor activity GO:0008528 G-protein coupled peptide receptor activity GO:0016494 C-X-C chemokine receptor activity GO:0019955 cytokine binding GO:0019956 chemokine binding
Cellular Component	GO:0009897 external side of plasma membrane GO:0098552 side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04062 Chemokine signaling pathway
Reactome	R-HSA-380108: Chemokine receptors bind chemokines R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-418594: G alpha (i) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-375276: Peptide ligand-binding receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CXCR3 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 CXCR3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26109379	Melanoma	Promote immunity (infiltration)	These studies unexpectedly reveal a non-redundant requirement for the CXCR3-CXCL9/CXCL10 axis for CD8+ T cell trafficking within the intravascular space that could not be predicted from static profiling of intratumoral chemokines or their receptors on T cells.
26075911	Melanoma	Promote immunity (infiltration)	Inhibition of DPP4 enzymatic activity enhanced tumor rejection by preserving biologically active CXCL10 and increasing trafficking into the tumor by lymphocytes expressing the counter-receptor CXCR3. Furthermore, DPP4 inhibition improved adjuvant-based immunotherapy, adoptive T cell transfer and checkpoint blockade.
26025380	Melanoma; Lung Carcinoma	Promote immunity (T cell function)	Together, our study reveals a negative regulation by STAT3 signaling in T cells on cross-talk between myeloid cells and T cells through IFNγ/CXCR3/CXCL10, which is important for CD8(+) T cells homing to tumors.
29316433	Breast carcinoma	Promote immunity	Gene expression analysis identified upregulation of Cxcl9 within intratumoral DCs during combination therapy, and therapeutic efficacy was ablated by CXCR3 blockade, Batf3 deficiency, or Irf8 deficiency.
21170961	Melanoma	Promote immunity (infiltration)	Enhanced Type-1 T cell infiltration of tumors was associated with treatment-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and CXCR3 ligand chemokines in vascular/peri-vascular cells within the TME, with SUT/VAC therapy benefits conditionally negated upon adminsitration of CXCR3 or VCAM-1 blocking antibodies.
16585565	Lung Carcinoma	Promote immunity	IFN-gamma acts on T cells to induce NK cell mobilization and accumulation in target organs. Intraperitoneal administration of IFN-gamma stimulates the mobilization of NK cells into the circulation, but not their cell death or proliferation. Moreover, mobilization and migration of spleen NK cells in response to IFN-gamma treatment is dependent on the chemokine receptor CXCR3.
27465528	B16 Malignant Melanoma	Promote immunity (infiltration)	Significant accelerations in tumor growth and reduced survival were observed in both BLT1(-/-) and CXCR3(-/-) mice as compared with wild-type (WT) mice. The loss of efficacy correlated with failure of the knockout CTLs to infiltrate into tumors upon anti-PD-1 treatment, suggesting an obligate requirement for both BLT1 and CXCR3 in mediating anti-PD-1 based antitumor immune response. These results demonstrate a critical role for both BLT1 and CXCR3 in CTL migration to tumors and thus may be targeted to enhance efficacy of CTL-based immunotherapies.
17785868	Primary Cutaneous T-Cell Non-Hodgkin Lymphoma	Promote immunity (infilration)	In this study, we show that advanced cutaneous T cell lymphoma (CTCL) is associated with selective and efficient inactivation of CXCR3-dependent T cell migration. Our studies demonstrate that this alteration is at least in part due to CXCR3 down-regulation in vivo by elevated serum levels of CXCR3 ligands. The T cell population most affected by this down-regulatory mechanism are CD8+ cytotoxic effector T cells. In CTCL patients, cytotoxic effector T cells have strongly reduced surface CXCR3 expression, accumulate in peripheral blood, but are virtually absent from CTCL tumor lesions, indicating an inability to extravasate into lymphoma tissue.
24893628	Skin Basal Cell Carcinoma	Promote immunity (T cell function); increase the efficacy of immunotherapy	Our results indicate that intramuscular CRT/E7 vaccination in conjunction with intravaginal imiquimod deposition recruits antigen-specific CXCR3(+) CD8(+) T cells to the genital tract.
22798340	Ovarian Carcinoma	Inhibit immunity	CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity. Here, we show that CXCR3(+) Treg are highly enriched in human ovarian carcinomas, particularly in solid tumor masses, where they represent the majority of Treg. Tumor-associated CXCR3(+.) Treg coexpress T-bet but do not secrete IFN-γ ex vivo and suppress proliferation and IFN-γ secretion of T effectors.
18922917	Lymphoma; Melanoma	Promote immunity (infiltration)	Accordingly, significantly lower numbers of tumor-infiltrating NK cells were detected in CXCR3(-/-) mice, and the capacity of adoptively transferred CXCR3(-/-) NK cells to accumulate in the tumor was severely impaired. Our results identify IFN-gamma and the expression of CXCR3 on NK cells as prerequisites for NK cell infiltration into tumors.
25212604	Anaplastic Thyroid Carcinoma	Promote immunity（NK cell infiltration)	Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3.
21792901	renal cell carcinoma; melanoma; colon carcinoma	Promote immunity (T cell function)	The CD8 tumor-infiltrating T lymphocytes in 6-gingerol-treated mice strongly expressed IFN-γ, a marker of activation of cytotoxic T lymphocytes (CTL) CD107a and chemokine receptors that are expressed on T(H) 1 cells, such as CXCR3 and CCR5.

Summary
Symbol	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
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 CXCR3 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	Sensitive to T cell-mediated killing
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
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 CXCR3 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	0.063	0.914
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.334	0.791
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.129	0.893
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.221	0.703
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.214	0.865
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.219	0.871
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.391	0.0695
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	2.148	0.0495
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.511	0.664
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.797	0.0368
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	1.42	0.286
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.013	0.96

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CXCR3 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	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	0	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	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	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	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
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	20	0	20	0.294

Summary
Symbol	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CXCR3. 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	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CXCR3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CXCR3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CXCR3. 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	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CXCR3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CXCR3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CXCR3
Name	chemokine (C-X-C motif) receptor 3
Aliases	CKR-L2; CMKAR3; IP10-R; MigR; CD183; GPR9; G protein-coupled receptor 9; Mig-R; IP-10 receptor; Mig receptor ......
Chromosomal Location	Xq13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CXCR3 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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