CCR8 (C-C Motif Chemokine Receptor 8): A Key Regulator of Immune Response and Therapeutic Target in Oncology
Comprehensive genomic and functional analysis of CCR8, a chemokine receptor with critical roles in Treg cell biology, cancer immunity, and inflammatory diseases.
Gene Information Card
| Symbol | CCR8 |
|---|---|
| Full Name | C-C Motif Chemokine Receptor 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p22.3 |
| NCBI Gene ID | 1237 ncbi.nlm.nih.gov/gene/1237 |
| Ensembl ID | ENSG00000179934 |
| UniProt ID | P51685 |
| OMIM ID | 601747 |
| HGNC ID | 1608 |
| Aliases | CMKBR8, CMKBRL2, CC-CKR-8, CCR-8, CDw198, GPRCY6, TER1, CKRL2 |
Description
CCR8 (C-C Motif Chemokine Receptor 8) is a G protein-coupled receptor (GPCR) that belongs to the CC chemokine receptor family. It is encoded by the CCR8 gene located on chromosome 3p22.3. CCR8 is a seven-transmembrane protein that primarily binds to the chemokine CCL1 (I-309). It is predominantly expressed on the surface of regulatory T cells (Tregs), Th2 cells, and certain tumor-infiltrating lymphocytes. CCR8 signaling plays a critical role in immune regulation, particularly in the recruitment and function of Tregs within the tumor microenvironment, where it contributes to immune evasion. This makes CCR8 a promising target for cancer immunotherapy. Additionally, CCR8 is involved in various inflammatory and autoimmune conditions, as well as in the pathogenesis of certain viral infections, serving as a co-receptor for HIV-1 entry.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | CCR8 is highly expressed on tumor-infiltrating Tregs, promoting their recruitment and suppressive function within the tumor microenvironment. This leads to immune evasion and poor prognosis. Targeting CCR8 can deplete intratumoral Tregs and enhance anti-tumor immunity. | High expression in TILs correlates with poor prognosis in breast, colorectal, and lung cancers. Preclinical models show anti-CCR8 antibodies deplete Tregs and inhibit tumor growth. |
| Inflammatory Bowel Disease (IBD) | CCR8 and its ligand CCL1 are upregulated in inflamed intestinal tissues. CCR8+ T cells contribute to the inflammatory cascade, promoting tissue damage and chronic inflammation. | Elevated CCR8 expression found in colonic biopsies from IBD patients. Animal models of colitis show reduced inflammation with CCR8 blockade. |
| Atopic Dermatitis | CCR8 is expressed on Th2 cells and Tregs, which are key players in the pathogenesis of atopic dermatitis. CCR8-mediated chemotaxis contributes to the accumulation of these cells in the skin lesions. | Increased CCR8+ cells in skin lesions of atopic dermatitis patients. CCR8-deficient mice show reduced skin inflammation in experimental models. |
| HIV-1 Infection | CCR8 can act as a co-receptor for certain strains of HIV-1, facilitating viral entry into CD4+ T cells. This is particularly relevant in the context of CCR5 and CXCR4 tropism. | In vitro studies demonstrate CCR8-dependent HIV-1 entry. CCR8 usage is more common in certain viral isolates and may contribute to pathogenesis. |
| Asthma | CCR8 is expressed on Th2 cells, which are central to allergic airway inflammation. CCR8 signaling promotes the migration of Th2 cells to the lungs, contributing to eosinophilia and airway hyperresponsiveness. | CCR8 expression is increased in the airways of asthmatic patients. CCR8 knockout mice are protected from allergen-induced airway inflammation. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph Node | 5.2 | Medium |
| Spleen | 4.8 | Medium |
| Appendix | 3.1 | Low |
| Bone Marrow | 2.5 | Low |
| Thymus | 2.0 | Low |
| Lung | 1.5 | Low |
| Small Intestine | 1.2 | Low |
| Colon | 1.0 | Low |
| Blood | 0.8 | Low |
| Skin | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Tregs (Regulatory T cells) | N/A | High expression; key for function |
| Th2 cells | N/A | Moderate expression |
| Jurkat (T cell leukemia) | 0.3 | Low expression |
| Ramos (Burkitt's lymphoma) | 0.1 | Very low expression |
| K-562 (CML) | 0.2 | Very low expression |
| A549 (Lung carcinoma) | 0.1 | Very low expression |
| MCF7 (Breast cancer) | 0.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.245C>T (p.Thr82Ile) | Missense | Rare (<0.01%) | Potential alteration in ligand binding or signaling; clinical significance unknown. |
| c.568G>A (p.Val190Met) | Missense | Rare (<0.01%) | Located in transmembrane domain; may affect receptor conformation and function. |
| c.821A>G (p.Asn274Ser) | Missense | Rare (<0.01%) | Potential impact on G-protein coupling or receptor desensitization. |
| c.937C>T (p.Arg313Trp) | Missense | Rare (<0.01%) | In the C-terminal tail; may affect phosphorylation sites and intracellular signaling. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CCR8 are rare and not well-characterized. They could impair receptor expression, ligand binding, or downstream signaling, potentially affecting Treg cell function and immune regulation. No specific pathogenic loss-of-function variants have been definitively established in human disease.
Gain of Function (GOF)
Gain-of-function mutations that enhance CCR8 signaling have not been clearly identified. However, overexpression of CCR8, rather than mutation, is the primary mechanism driving its oncogenic and immunosuppressive roles in cancer.
Dominant Negative (DN)
No dominant-negative mutations have been described for CCR8. Given its GPCR structure, such mutations would likely interfere with receptor dimerization or signaling, but this has not been experimentally demonstrated.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • C-C chemokine receptor activity |
| • C-C chemokine binding | • Signal transducer activity |
| • Cell surface receptor signaling pathway | • Chemokine-mediated signaling pathway |
| • Immune response | • Cell chemotaxis |
| • Inflammatory response | • Positive regulation of cytosolic calcium ion concentration |
| • Regulation of cell population proliferation |
Pathways
• Chemokine signaling pathway (KEGG: hsa04062)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
• T cell receptor signaling pathway (KEGG: hsa04660)
• G alpha (i) signaling events (Reactome: R-HSA-418594)
• Peptide ligand-binding receptors (Reactome: R-HSA-375276)
Protein Summary
CCR8 is a 355-amino acid protein with a molecular weight of approximately 40.5 kDa. It is a member of the class A rhodopsin-like GPCR family, characterized by seven transmembrane alpha-helices, an extracellular N-terminus, and an intracellular C-terminus. The protein structure includes conserved motifs essential for G-protein coupling and receptor activation. CCR8 primarily signals through G-alpha-i proteins, leading to inhibition of adenylate cyclase, activation of phospholipase C, and increases in intracellular calcium. The N-terminal domain is involved in ligand binding, while the intracellular loops and C-terminal tail contain phosphorylation sites critical for receptor desensitization and internalization. CCR8 is expressed as a monomer but may form homodimers or heterodimers with other chemokine receptors, modulating its function. Post-translational modifications, such as glycosylation, may also affect receptor trafficking and ligand affinity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CCR8 Knockout HEK293 Cell Line | EDJ-KQ3618 | Human | 1237 | Details Get a Quote |
| CCR8 Knockout HeLa Cell Line | EDJ-KQ52936 | Human | 1237 | Details Get a Quote |
| CCR8 Knockout A-549 Cell Line | EDJ-KQ61403 | Human | 1237 | Details Get a Quote |
| CCR8 Knockout HCT 116 Cell Line | EDJ-KQ69898 | Human | 1237 | Details Get a Quote |
| CCR8 Overexpression HEK293 Stable Cell Line | EDJ-GQ89 | Human | 1237 | Details Get a Quote |
| CCR8 Overexpression HEK293T Stable Cell Line | EDJ-GQ90 | Human | 1237 | Details Get a Quote |
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