TISIDB

Summary
Symbol	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
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	Involved in neutrophil activation. In vitro, ENA-78(8-78) and ENA-78(9-78) show a threefold higher chemotactic activity for neutrophil granulocytes.

> Gene Ontology [ TOP ]
Biological Process	GO:0002237 response to molecule of bacterial origin GO:0002443 leukocyte mediated immunity GO:0002444 myeloid leukocyte mediated immunity GO:0002446 neutrophil mediated immunity 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:0030335 positive regulation of cell migration GO:0030595 leukocyte chemotaxis GO:0032103 positive regulation of response to external stimulus GO:0032496 response to lipopolysaccharide GO:0040017 positive regulation of locomotion GO:0050900 leukocyte migration GO:0050920 regulation of chemotaxis GO:0050921 positive regulation of chemotaxis GO:0051272 positive regulation of cellular component movement GO:0060326 cell chemotaxis GO:0070098 chemokine-mediated signaling pathway 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
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04062 Chemokine signaling pathway hsa04668 TNF 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	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CXCL5 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 CXCL5 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24525743	Hepatocellular carcinoma	Inhibit immunity (T cell function)	Mechanistic investigations showed that IL-17A induced CXCL5 production by tumor cells to enhance the infiltration of myeloid-derived suppressor cells (MDSC) to tumor sites in a CXCL5/CXCR2-dependent manner.
29036438	Gastric Carcinoma	Inhibit immunity (T cell function)	We generated a xenograft mouse model and used SEW-2871, a S1P1 specific agonist to activate S1P1 signalling. SEW-2871 promoted tumor growth in our mouse model, and induced a higher level of MDSC and a reduced level of CD8+CD69+ T cells within tumor. Additionally, SEW-2871 enhanced expression of several MDSC recruitment-associated chemokines (CXCL12, CXCL5 and CCL2) in tumor cells. These chemokines facilitated MDSC migration by interaction with CCR2, CXCR2 and CXCR4. S1P1 signalling promoted gastric cancer by enhancing chemokine expression in tumor cells and recruiting MDSC to tumor microenvironment, which impaired anti-tumoral function of TILs.
23737434	Breast Carcinoma	Inhibit immunity (T cell function)	Finally, we found that CXCL5/CXCR2 axis facilitated MDSC migration and that anti-GM-CSF antibodies neutralized CXCL5-induced accumulation of MDSCs. Taken together, our data suggest that KLF4 modulates maintenance of MDSCs in bone marrow by inducing GM-CSF production via CXCL5 and regulates recruitment of MDSCs into the primary tumors through the CXCL5/CXCR2 axis, both of which contribute to KLF4-mediated mammary tumor development.
27737879	Pancreatic Ductal Adenocarcinoma	Inhibit immunity (T cell function)	CXCL5 was the most prominently expressed CXCR2 ligand in human PDA, and its expression was higher in PDA than in any other common tumor represented in The Cancer Genome Atlas. Cxcl5 expression was associated with mutant Kras expression and regulated by NF-κB activation.
24346967	Lung Carcinoma	Inhibit immunity; Resistant to immunotherapy	CXCL5 not only potentiated the classical EGFR pathway and the AKT and ERK/RSK1/2 signaling pathways but also increased the phosphorylation of heat shock protein 27 (HSP27), which was slightly increased in A549 cells treated with either HB-EGF or CXCL5 only. Phosphorylated HSP27 stabilized sustained AKT activity by direct interaction, leading to enhanced tumor spheroid formation. In mice, CXCL5 antibody synergistically enhances the efficiency of the tyrosine kinase inhibitor, gefitinib, without increasing its toxicity.

Summary
Symbol	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
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 CXCL5 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	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
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 CXCL5 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	-1.002	0.189
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.275	0.301
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.805	0.446
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-2.518	0.00926
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-3.61	0.00552
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.114	0.522
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.1	0.905
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-1.4	0.237
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.445	0.253
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	2.652	0.04
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	2.424	0.205
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.128	0.745

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CXCL5 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	0	0	1
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	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
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	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
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	9.1	-9.1	0.458
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	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
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	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	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CXCL5. 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	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CXCL5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CXCL5. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CXCL5. 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	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CXCL5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CXCL5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CXCL5
Name	chemokine (C-X-C motif) ligand 5
Aliases	ENA-78; SCYB5; small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil-act ......
Chromosomal Location	4q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CXCL5 collected from DrugBank database.

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

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