Browse CCR4

Summary
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
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
 
Subcellular Location Cell membrane; Multi-pass membrane protein.
Domain PF00001 7 transmembrane receptor (rhodopsin family)
Function

High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calcium second messenger system. Can function as a chemoattractant homing receptor on circulating memory lymphocytes and as a coreceptor for some primary HIV-2 isolates. In the CNS, could mediate hippocampal-neuron survival.

> Gene Ontology
 
Biological Process GO:0001764 neuron migration
GO:0002507 tolerance induction
GO:0006874 cellular calcium ion homeostasis
GO:0006875 cellular metal ion homeostasis
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0009314 response to radiation
GO:0032103 positive regulation of response to external stimulus
GO:0040017 positive regulation of locomotion
GO:0046677 response to antibiotic
GO:0048872 homeostasis of number of cells
GO:0050918 positive chemotaxis
GO:0050920 regulation of chemotaxis
GO:0050921 positive regulation of chemotaxis
GO:0050926 regulation of positive chemotaxis
GO:0050927 positive regulation of positive chemotaxis
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:0016493 C-C chemokine receptor activity
Cellular Component GO:0009897 external side of plasma membrane
GO:0043025 neuronal cell body
GO:0044297 cell body
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
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CCR4 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 CCR4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
19377047Hodgkin lymphomaPromote immunityWe now show that forced expression of CCR4 by effector T cells enhances their migration to HL cells. Furthermore, T lymphocytes expressing both CCR4 and a chimeric antigen receptor directed to the HL associated antigen CD30 sustain their cytotoxic function and cytokine secretion in vitro, and produce enhanced tumor control when infused intravenously in mice engrafted with human HL.
19377047Hodgkin lymphomaPromote immunityBy contrast, effector CD8(+) T cells lack CCR4, are nonresponsive to these chemokines and are rarely detected at the tumor site. We now show that forced expression of CCR4 by effector T cells enhances their migration to HL cells. Furthermore, T lymphocytes expressing both CCR4 and a chimeric antigen receptor directed to the HL associated antigen CD30 sustain their cytotoxic function and cytokine secretion in vitro, and produce enhanced tumor control when infused intravenously in mice engrafted with human HL.
23686488Follicular LymphomaInhibit immunityTumor supernatants induced preferential migration of Tregs and IL-4-producing T cells rather than IFN-γ-producing T cells, and Abs to CCR4 significantly abrogated the migration of Tregs.
20160057Adult T-Cell Leukemia/LymphomaInhibit immunityWe have developed the humanized defucosylated anti-CC chemokine receptor 4 (CCR4) monoclonal antibody KW-0761 as a next generation immunotherapeutic agent. The degree of KW-0761 ADCC against primary ATLL cells in an autologous setting was mainly determined by the amount of effector natural killer cells present, but not the amount of the target molecule CCR4 on the ATLL cell surface. KW-0761 should be sufficiently active for therapeutic clinical application for ATLL.
24127572MelanomaInhibit immunityAnti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. In melanoma tissues, CCR4(+) eTreg cells were predominant among tumor-infiltrating FOXP3(+) T cells and much higher in frequency compared with those in peripheral blood. With peripheral blood lymphocytes from healthy individuals and melanoma patients, ex vivo depletion of CCR4(+) T cells and subsequent in vitro stimulation of the depleted cell population with the cancer/testis antigen NY-ESO-1 efficiently induced NY-ESO-1-specific CD4(+) T cells. CCR4(+) T-cell depletion also augmented in vitro induction of NY-ESO-1-specific CD8(+) T cells in melanoma patients.
22869555Primary Cutaneous T-Cell Non-Hodgkin LymphomaInhibit immunityHumanization of an anti-CCR4 antibody that kills cutaneous T-cell lymphoma cells and abrogates suppression by T-regulatory cells. CCR4 is also highly expressed on T-regulatory cells (Tregs) that can migrate to several different types of chemotactic ligand CCL17- and CCL22-secreting tumors to facilitate tumor cell evasion from immune surveillance. Moreover, mAb1567 also effectively inhibits chemotaxis of CD4(+)CD25(high) Tregs via CCL22 and abrogates Treg suppression activity in vitro.
Summary
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
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
  Statistical results of CCR4 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/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
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
 
Points in the above scatter plot represent the expression difference of CCR4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0150.966
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.0420.944
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0010.998
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.5510.244
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.7880.483
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.250.855
729033130MelanomaallAnti-PD-1 (nivolumab) 26231.1310.0576
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.7010.0527
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.4650.618
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.0170.0578
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.7430.316
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.5470.0279
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CCR4 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) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
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) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CCR4. 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
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CCR4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CCR4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CCR4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CCR4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CCR4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCCR4
Namechemokine (C-C motif) receptor 4
Aliases CC-CKR-4; CMKBR4; CKR4; k5-5; CD194; HGCN:14099; C-C CKR-4; CCR-4; chemokine (C-C) receptor 4; CD antigen CD ......
Chromosomal Location3p24-p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CCR4 collected from DrugBank database.
> Drugs from DrugBank database
 

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