TISIDB

Summary
Symbol	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
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	Secreted.
Domain	PF00048 Small cytokines (intecrine/chemokine)
Function	Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3.

> Gene Ontology [ TOP ]
Biological Process	GO:0000768 syncytium formation by plasma membrane fusion GO:0002237 response to molecule of bacterial origin GO:0002685 regulation of leukocyte migration GO:0002687 positive regulation of leukocyte migration GO:0002688 regulation of leukocyte chemotaxis GO:0002690 positive regulation of leukocyte chemotaxis GO:0006140 regulation of nucleotide metabolic process GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006949 syncytium formation GO:0006968 cellular defense response GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007520 myoblast fusion GO:0009150 purine ribonucleotide metabolic process GO:0009187 cyclic nucleotide metabolic process GO:0009615 response to virus GO:0010522 regulation of calcium ion transport into cytosol GO:0010524 positive regulation of calcium ion transport into cytosol GO:0010830 regulation of myotube differentiation GO:0010831 positive regulation of myotube differentiation GO:0010959 regulation of metal ion transport GO:0014902 myotube differentiation GO:0019932 second-messenger-mediated signaling GO:0019933 cAMP-mediated signaling GO:0019935 cyclic-nucleotide-mediated signaling GO:0030335 positive regulation of cell migration GO:0030595 leukocyte chemotaxis GO:0030799 regulation of cyclic nucleotide metabolic process GO:0030801 positive regulation of cyclic nucleotide metabolic process GO:0030814 regulation of cAMP metabolic process GO:0030816 positive regulation of cAMP metabolic process GO:0032103 positive regulation of response to external stimulus GO:0032496 response to lipopolysaccharide GO:0032844 regulation of homeostatic process GO:0032845 negative regulation of homeostatic process GO:0032846 positive regulation of homeostatic process GO:0034762 regulation of transmembrane transport GO:0034764 positive regulation of transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0034767 positive regulation of ion transmembrane transport GO:0040017 positive regulation of locomotion GO:0042692 muscle cell differentiation GO:0043270 positive regulation of ion transport GO:0043949 regulation of cAMP-mediated signaling GO:0043950 positive regulation of cAMP-mediated signaling GO:0045445 myoblast differentiation GO:0045661 regulation of myoblast differentiation GO:0045663 positive regulation of myoblast differentiation GO:0045981 positive regulation of nucleotide metabolic process GO:0046058 cAMP metabolic process GO:0050900 leukocyte migration GO:0050920 regulation of chemotaxis GO:0050921 positive regulation of chemotaxis GO:0051146 striated muscle cell differentiation GO:0051147 regulation of muscle cell differentiation GO:0051149 positive regulation of muscle cell differentiation GO:0051153 regulation of striated muscle cell differentiation GO:0051155 positive regulation of striated muscle cell differentiation GO:0051208 sequestering of calcium ion GO:0051209 release of sequestered calcium ion into cytosol GO:0051235 maintenance of location GO:0051238 sequestering of metal ion GO:0051272 positive regulation of cellular component movement GO:0051279 regulation of release of sequestered calcium ion into cytosol GO:0051281 positive regulation of release of sequestered calcium ion into cytosol GO:0051282 regulation of sequestering of calcium ion GO:0051283 negative regulation of sequestering of calcium ion GO:0051480 regulation of cytosolic calcium ion concentration GO:0051607 defense response to virus GO:0051924 regulation of calcium ion transport GO:0051928 positive regulation of calcium ion transport GO:0055074 calcium ion homeostasis GO:0060142 regulation of syncytium formation by plasma membrane fusion GO:0060143 positive regulation of syncytium formation by plasma membrane fusion GO:0060326 cell chemotaxis GO:0060401 cytosolic calcium ion transport GO:0060402 calcium ion transport into cytosol GO:0070098 chemokine-mediated signaling pathway GO:0070509 calcium ion import GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport GO:0090279 regulation of calcium ion import GO:0090280 positive regulation of calcium ion import GO:0097553 calcium ion transmembrane import into cytosol GO:0098542 defense response to other organism GO:1900542 regulation of purine nucleotide metabolic process GO:1900544 positive regulation of purine nucleotide metabolic process GO:1901739 regulation of myoblast fusion GO:1901741 positive regulation of myoblast fusion GO:1902656 calcium ion import into cytosol GO:1903169 regulation of calcium ion transmembrane transport GO:1904062 regulation of cation transmembrane transport GO:1904064 positive regulation of cation transmembrane transport GO:1904427 positive regulation of calcium ion transmembrane transport GO:2000021 regulation of ion homeostasis GO:2000147 positive regulation of cell motility
Molecular Function	GO:0001664 G-protein coupled receptor binding GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0008009 chemokine activity GO:0042379 chemokine receptor binding GO:0045236 CXCR chemokine receptor binding GO:0048248 CXCR3 chemokine receptor 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 hsa04620 Toll-like receptor 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	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CXCL9 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 CXCL9 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26567139	Colon Carcinoma	Promote immunity (infiltration)	We found that PRC2 components and demethylase JMJD3-mediated histone H3 lysine 27 trimethylation (H3K27me3) repress the expression and subsequent production of Th1-type chemokines CXCL9 and CXCL10, mediators of effector T-cell trafficking. Moreover, the expression levels of PRC2 components, including EZH2, SUZ12, and EED, were inversely associated with those of CD4, CD8, and Th1-type chemokines in human colon cancer tissue, and this expression pattern was significantly associated with patient survival.
26503055	Ovarian Carcinoma	Promote immunity (infiltration)	Using human ovarian cancers as our model, here we show that enhancer of zeste homologue 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27me3) and DNA methyltransferase 1 (DNMT1)-mediated DNA methylation repress the tumour production of T helper 1 (TH1)-type chemokines CXCL9 and CXCL10, and subsequently determine effector T-cell trafficking to the tumour microenvironment.
27070705	Colorectal Carcinoma	Promote immunity (infiltration)	While two distinct subsets of myeloid cells induce an influx of T cells into the invasive margin via CXCL9/CXCL10, CCL5 is produced by these T cells and stimulates pro-tumoral effects via CCR5.
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.
25754875	Colorectal Carcinoma	Promote immunity (infiltration)	We also demonstrate a selective increase of the chemokines CXCL9 and CXCL10 in Treg-cell-depleted tumors, which were accompanied by accumulation of CXCR3(+) T cells, and increased IFN-γ mRNA expression.
25398437	Melanoma	Promote immunity	Here we show how combining a senescence-inducing inhibitor of the mitotic kinase Aurora A (AURKA) with an MDM2 antagonist activates p53 in senescent tumors harboring wildtype 53. In the model studied, this effect is accompanied proliferation arrest, mitochondrial depolarization, apoptosis and immune clearance of cancer cells by antitumor leukocytes in a manner reliant upon CCL5, CCL1 and CXCL9.
28486109	Melanoma	Promote immunity (infiltration)	Mechanistically, this was due to the absence of CXCL9/10, which we found to be produced by CD103+dendritic cells (DCs) in T?cell-inflamed tumors. Our data indicate that lack of CD103+DCs within the tumor microenvironment dominantly resists the effector phase of an anti-tumor T?cell response, contributing to immune escape.
19470694	Ovarian Carcinoma	Promote immunity (infiltration)	Furthermore, through synergistic action between IL-17 and interferon-gamma, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome.
22333315	Breast Carcinoma	Promote immunity (infiltration)	In murine breast cancer models, the two interferon-gamma (IFN-γ) inducible chemokines and CXC-chemokine receptor 3 (CXCR3) receptor ligands, monokine induced by γ-interferon (CXCL9) and interferon-γ-inducible protein-10 (CXCL10) impair tumor growth and metastasis formation through recruitment of natural killer (NK) cells and tumor-suppressive T lymphocytes.
24893628	Skin Basal Cell Carcinoma	Promote immunity (infiltration)	Intravaginal imiquimod deposition induced upregulation of CXCL9 and CXCL10 mRNA expression in the genital tract, which are produced in response to IFNγ receptor signaling and attract cells expressing their ligand, CXCR3.
29671006	Colon Carcinoma	Promote immunity (infiltration)	Treg depletion also resulted in increased levels of the chemokines CXCL9 and CXCL10 specifically in the tumors.
24004819	Breast Carcinoma	Promote immunity (infiltration)	Enhanced immune surveillance in COX-2(MEC)KO tumors was coincident with increased intratumoral CXCL9, a T cell chemoattractant, and decreased expression of T lymphocyte co-inhibitory receptors CTLA4 and PD-1, as well as PD-L1, the ligand for PD-1.
23843024	Breast Carcinoma	Promote immunity (infiltration)	Furthermore, Stat1-deficiency resulted in reduced expression of the T-cell chemotactic factors CXCL9, CXCL10, and CXCL11 in the tumor epithelium.
25092771	colon carcinoma	Promote immunity	This combination therapy also increased TILs, including tumor antigen-specific CD8 T cells, and elevated the expression of activation markers FAS-L, CXCL-9, CD31, and CD105 in MDSCs and TAMs, leading to reduced tumor volumes and an increase in the number of tumor-free animals.
23241877	fibrosarcoma	Promote immunity	Remarkably, the ability of Mig-deficient tumor cells to express another CXCR3 ligand, CXCL10/IFN-gamma-inducible protein, does not compensate for the absent antitumor functions of Mig, suggesting a nonredundant role for this chemokine in the suppression of tumor growth.
21949133	Lung Carcinoma	Promote immunity	Increased apoptosis, the induction of cytokines (IFN-γ and IL-12) and chemokines (CXCL9 and CXCL10), and the elevation of leukocyte markers (CD11b, CD11c, CD4, and CD8) were detected at tumor sites in C3H/HeN mice but not in C3H/HeJ mice

Summary
Symbol	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
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

[ TOP ]

Statistical results of CXCL9 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	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
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

[ TOP ]

Points in the above scatter plot represent the expression difference of CXCL9 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	-0.122	0.896
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.396	0.878
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.496	0.796
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.935	0.352
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	1.991	0.207
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.397	0.834
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.373	0.0853
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.918	0.295
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.721	0.732
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	2.02	0.283
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	1.981	0.506
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	1.294	0.000485

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CXCL9 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CXCL9. 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	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CXCL9. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CXCL9. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CXCL9. 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	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CXCL9 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CXCL9 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CXCL9
Name	chemokine (C-X-C motif) ligand 9
Aliases	SCYB9; Humig; crg-10; MIG; monokine induced by gamma interferon; gamma-interferon-induced monokine; monokine ......
Chromosomal Location	4q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CXCL9 collected from DrugBank database.

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

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