Browse CXCR3

Summary
SymbolCXCR3
Namechemokine (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 LocationXq13
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 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
 
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
 
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
SymbolCXCR3
Namechemokine (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 LocationXq13
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
 
  Literatures describing the relation between CXCR3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26109379MelanomaPromote 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.
26075911MelanomaPromote 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.
26025380Melanoma; Lung CarcinomaPromote 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.
29316433Breast carcinomaPromote immunityGene 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.
21170961MelanomaPromote 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.
16585565Lung CarcinomaPromote immunityIFN-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.
27465528B16 Malignant MelanomaPromote 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.
17785868Primary Cutaneous T-Cell Non-Hodgkin LymphomaPromote 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.
24893628Skin Basal Cell CarcinomaPromote immunity (T cell function); increase the efficacy of immunotherapyOur results indicate that intramuscular CRT/E7 vaccination in conjunction with intravaginal imiquimod deposition recruits antigen-specific CXCR3(+) CD8(+) T cells to the genital tract.
22798340Ovarian CarcinomaInhibit immunityCXCR3+ 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.
18922917Lymphoma; MelanomaPromote 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.
25212604Anaplastic Thyroid CarcinomaPromote 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.
21792901renal cell carcinoma; melanoma; colon carcinomaPromote 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
SymbolCXCR3
Namechemokine (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 LocationXq13
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 CXCR3 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/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA Sensitive to T cell-mediated killing
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolCXCR3
Namechemokine (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 LocationXq13
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 CXCR3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0630.914
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.3340.791
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1290.893
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2210.703
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.2140.865
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2190.871
729033130MelanomaallAnti-PD-1 (nivolumab) 26231.3910.0695
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15112.1480.0495
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.5110.664
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.7970.0368
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.420.286
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0130.96
> Mutation difference between responders and non-responders
 
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 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) 103033.3-33.30.231
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
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) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382703.7-3.70.415
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221307.7-7.70.371
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 512200200.294
Summary
SymbolCXCR3
Namechemokine (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 LocationXq13
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
 
Summary
SymbolCXCR3
Namechemokine (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 LocationXq13
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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCXCR3
Namechemokine (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 LocationXq13
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
 
> Receptor
 
Summary
SymbolCXCR3
Namechemokine (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 LocationXq13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CXCR3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCXCR3
Namechemokine (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 LocationXq13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CXCR3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCXCR3
Namechemokine (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 LocationXq13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CXCR3 collected from DrugBank database.
> Drugs from DrugBank database
 

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