TISIDB

Summary
Symbol	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
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; Multi-pass membrane protein.
Domain	PF00001 7 transmembrane receptor (rhodopsin family)
Function	Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001655 urogenital system development GO:0001656 metanephros development GO:0001776 leukocyte homeostasis GO:0001780 neutrophil homeostasis GO:0001781 neutrophil apoptotic process GO:0001822 kidney development GO:0002262 myeloid cell homeostasis GO:0002274 myeloid leukocyte activation GO:0002407 dendritic cell chemotaxis GO:0002437 inflammatory response to antigenic stimulus GO:0002438 acute inflammatory response to antigenic stimulus GO:0002526 acute inflammatory response GO:0002683 negative regulation of immune system process 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:0003013 circulatory system process GO:0003018 vascular process in circulatory system GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006898 receptor-mediated endocytosis GO:0006925 inflammatory cell apoptotic process GO:0006968 cellular defense response GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0008015 blood circulation GO:0010657 muscle cell apoptotic process GO:0010658 striated muscle cell apoptotic process GO:0010659 cardiac muscle cell apoptotic process GO:0010660 regulation of muscle cell apoptotic process GO:0010661 positive regulation of muscle cell apoptotic process GO:0010662 regulation of striated muscle cell apoptotic process GO:0010663 positive regulation of striated muscle cell apoptotic process GO:0010665 regulation of cardiac muscle cell apoptotic process GO:0010666 positive regulation of cardiac muscle cell apoptotic process GO:0030335 positive regulation of cell migration GO:0030593 neutrophil chemotaxis GO:0030595 leukocyte chemotaxis GO:0030901 midbrain development GO:0031623 receptor internalization GO:0032103 positive regulation of response to external stimulus GO:0032844 regulation of homeostatic process GO:0032845 negative regulation of homeostatic process GO:0033028 myeloid cell apoptotic process GO:0033029 regulation of neutrophil apoptotic process GO:0033030 negative regulation of neutrophil apoptotic process GO:0033032 regulation of myeloid cell apoptotic process GO:0033033 negative regulation of myeloid cell apoptotic process GO:0035239 tube morphogenesis GO:0036230 granulocyte activation GO:0036336 dendritic cell migration GO:0038112 interleukin-8-mediated signaling pathway GO:0040017 positive regulation of locomotion GO:0042119 neutrophil activation GO:0043112 receptor metabolic process GO:0043114 regulation of vascular permeability GO:0043117 positive regulation of vascular permeability GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0048514 blood vessel morphogenesis GO:0048872 homeostasis of number of cells GO:0050900 leukocyte migration GO:0050920 regulation of chemotaxis GO:0050921 positive regulation of chemotaxis GO:0051272 positive regulation of cellular component movement GO:0051480 regulation of cytosolic calcium ion concentration GO:0055074 calcium ion homeostasis GO:0060326 cell chemotaxis GO:0060562 epithelial tube morphogenesis GO:0070098 chemokine-mediated signaling pathway GO:0071621 granulocyte chemotaxis GO:0071622 regulation of granulocyte chemotaxis GO:0071624 positive regulation of granulocyte chemotaxis GO:0071887 leukocyte apoptotic process GO:0072001 renal system development GO:0072073 kidney epithelium development GO:0072170 metanephric tubule development GO:0072173 metanephric tubule morphogenesis GO:0072207 metanephric epithelium development GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0090022 regulation of neutrophil chemotaxis GO:0090023 positive regulation of neutrophil chemotaxis GO:0097529 myeloid leukocyte migration GO:0097530 granulocyte migration GO:0098758 response to interleukin-8 GO:0098759 cellular response to interleukin-8 GO:1901342 regulation of vasculature development GO:1902622 regulation of neutrophil migration GO:1902624 positive regulation of neutrophil migration GO:1904018 positive regulation of vasculature development GO:1990266 neutrophil migration GO:2000106 regulation of leukocyte apoptotic process GO:2000107 negative regulation of leukocyte apoptotic process GO:2000147 positive regulation of cell motility
Molecular Function	GO:0001637 G-protein coupled chemoattractant receptor activity GO:0001653 peptide receptor activity GO:0004896 cytokine receptor activity GO:0004918 interleukin-8 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 GO:0019958 C-X-C chemokine binding GO:0019959 interleukin-8 binding
Cellular Component	GO:0042629 mast cell granule

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04062 Chemokine signaling pathway hsa04144 Endocytosis
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-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6798695: Neutrophil degranulation R-HSA-375276: Peptide ligand-binding receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04060 Cytokine-cytokine receptor interaction
hsa04062 Chemokine signaling pathway
hsa04144 Endocytosis

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-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-6798695: Neutrophil degranulation
R-HSA-375276: Peptide ligand-binding receptors
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR

Summary
Symbol	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CXCR2 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 CXCR2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25349304	Non-Small Cell Lung Carcinoma	Inhibit immunity (T cell function)	miR141-CXCL1-CXCR2 signaling-induced Treg recruitment regulates metastases and survival of non-small cell lung cancer. Mechanistically, decreased expressions of miR141, associated with the survival of patients with NSCLC with MPE, resulted in the increased production of CXCL1 and recruitment of Tregs to promote immune escape of tumor.
27265504	Pancreatic ductal adenocarcinoma	Inhibit immunity	Importantly, loss or inhibition of CXCR2 improved T?cell entry, and combined inhibition of CXCR2 and PD1 in mice with established disease significantly extended survival. We show that CXCR2 signaling in the myeloid compartment can promote pancreatic tumorigenesis and is required for pancreatic cancer metastasis, making it an excellent therapeutic target.
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.
24848257	Rhabdomyosarcoma	Inhibit immunity (T cell fcuntion)	RMS induced robust expansion of CXCR2(+)CD11b(+)Ly6G(hi) MDSCs, and CXCR2 deficiency prevented CD11b(+)Ly6G(hi) MDSC trafficking to the tumor. When tumor trafficking of MDSCs was inhibited by CXCR2 deficiency, or after anti-CXCR2 monoclonal antibody therapy, delayed anti-PD1 treatment induced significant antitumor effects. Thus, CXCR2(+)CD11b(+)Ly6G(hi) MDSCs mediate local immunosuppression, which limits the efficacy of checkpoint blockade in murine RMS. Human pediatric sarcomas also produce CXCR2 ligands, including CXCL8. Patients with metastatic pediatric sarcomas display elevated serum CXCR2 ligands, and elevated CXCL8 is associated with diminished survival in this population. We conclude that accumulation of MDSCs in the tumor bed limits the efficacy of checkpoint blockade in cancer. We also identify CXCR2 as a novel target for modulating tumor immune escape and present evidence that CXCR2(+)CD11b(+)Ly6G(hi) MDSCs are an important suppressive myeloid subset in pediatric sarcomas
29632317	carcinoma	Inhibit immunity	Treatment of mice engrafted with wild-type EO771 cells with a Cxcr2 antagonist impaired tumor growth, reduced myeloid-derived suppressor cells and regulatory T cells, while increasing macrophages, dendritic cells, NK cells and the penetration of CD8+ T cells into the tumor bed.
27737879	Pancreatic Ductal Adenocarcinoma	Inhibit immunity (T cell function)	Evidence from various murine models has shown that the chemokine receptor CXCR2 attracts neutrophil into tumors and, therefore, represents a tractable therapeutic target. Host CXCR2 inhibition by genetic ablation prevented neutrophil accumulation in pancreatic tumors and led to a T cell-dependent suppression of tumor growth. In the absence of neutrophils, activated and functional T cells infiltrated pancreatic tumors otherwise devoid of effector T cells. Thus, the CXCR2-ligand axis helps establish an immunosuppressive microenvironment in PDA, highlighting the potential utility of targeting this axis as a novel therapy for this deadly disease.

Summary
Symbol	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
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 CXCR2 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	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
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 CXCR2 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	0.354	0.518
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.027	0.976
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.583	0.443
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.145	0.0815
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-2.389	0.03
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.428	0.751
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.191	0.797
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.381	0.728
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.335	0.758
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.253	0.254
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	0.791	0.617
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.294	0.177

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CXCR2 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	7.4	1.4	6	0.177
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	7.4	1.7	5.7	0.231
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	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CXCR2. 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	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CXCR2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CXCR2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CXCR2. 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	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CXCR2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CXCR2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CXCR2
Name	chemokine (C-X-C motif) receptor 2
Aliases	CMKAR2; IL8RB; interleukin 8 receptor, beta; CDw128b; IL8R2; CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor typ ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CXCR2 collected from DrugBank database.

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

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