TISIDB

Summary
Symbol	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
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 the chemokine CCL1/SCYA1/I-309. May regulate monocyte chemotaxis and thymic cell line apoptosis. Alternative coreceptor with CD4 for HIV-1 infection.

> Gene Ontology [ TOP ]
Biological Process	GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0051480 regulation of cytosolic calcium ion concentration GO:0055074 calcium ion homeostasis GO:0070098 chemokine-mediated signaling pathway GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis
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:0015026 coreceptor activity GO:0016493 C-C chemokine receptor activity
Cellular Component	-

> 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	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CCR8 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 CCR8 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18434408	Kaposi Sarcoma	Inhibit immunity	Human herpesvirus 8 (HHV-8), which is associated with the endothelial tumor Kaposi's sarcoma, encodes three CC/beta-chemokines. These are expressed early during productive (lytic) infection and are believed to be involved in immune evasion, in addition to viral pathogenesis via induction of angiogenic cytokines. Here we report that two of the HHV-8 chemokines, CCR8 agonists vCCL-1 and vCCL-2, have direct effects on endothelial survival and virus replication.
27851914	Colorectal Carcinoma; Small Cell Lung Cancinoma	Inhibit immunity	Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or non-small-cell lung cancers were compared to transcriptomes of the same subsets from normal tissues and validated at the single-cell level. We found that tumor-infiltrating Treg cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2 (IL1R2), programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine, which were not previously described on Treg cells.
23363815	Bladder Carcinoma; Renal cell Carcinoma	Inhibit immunity	Elevated secretion of CCL1 by tumors and increased presence of CCR8(+) myeloid cells in peripheral blood and cancer tissues indicate that CCL1/CCR8 axis is a component of cancer-related inflammation and may contribute to immune evasion.

Summary
Symbol	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
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 CCR8 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	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
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 CCR8 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	-0.1	0.69
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.062	0.898
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.127	0.752
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.74	0.243
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.134	0.894
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.856	0.102
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.737	0.32
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.342	0.782
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.093	0.385
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.838	0.124
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	0.127	0.855
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.141	0.572

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CCR8 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% 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	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	16.7	-16.7	0.429
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	0	0	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	0	0	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	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CCR8. 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	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CCR8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CCR8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CCR8. 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	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CCR8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CCR8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CCR8
Name	chemokine (C-C motif) receptor 8
Aliases	CY6; TER1; CKR-L1; GPR-CY6; CDw198; CMKBRL2; CMKBR8; CC-CKR-8; CCR-8; CKRL1; GPRCY6; CC chemokine receptor 8 ......
Chromosomal Location	3p22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CCR8 collected from DrugBank database.

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

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