C-C chemokine receptor type 8 (CCR8) (CCR8)

C-C chemokine receptor type 8 (CCR8) is a G protein-coupled receptor (GPCR) that has emerged as a high-priority novel target for cancer immunotherapy due to its highly restricted expression on tumor-infiltrating regulatory T cells (tiTregs) compared to peripheral Tregs or effector T cells (Cancer Cell, 2021). Its primary biological function involves mediating the migration and positioning of these suppressive cells in response to its ligand, CCL1, which is often overexpressed in the tumor microenvironment (TME) to facilitate immune evasion (Immunity, 2021). Unlike broader Treg markers such as CD25 or CTLA-4, targeting CCR8 allows for the selective depletion of the most suppressive T cells within a tumor, potentially reducing systemic autoimmune side effects while enhancing anti-tumor immunity. Therapeutic strategies primarily utilize monoclonal antibodies designed to deplete tiTregs via antibody-dependent cellular cytotoxicity (ADCC) or to block the recruitment of new Tregs into the tumor. Several pharmaceutical companies are currently evaluating anti-CCR8 agents in clinical trials, both as monotherapies and in combination with PD-1/PD-L1 inhibitors, to treat solid tumors that are resistant to current standard-of-care immunotherapies (J. Immunother. Cancer, 2023).

Other names

CCR8CDw198CY6CKRL1GPR-CY6TER1C-C CKR-8CMKBR8

Selective depletion of tumor-infiltrating regulatory T cells (tiTregs) via antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP), and/or blockade of CCR8-mediated recruitment of Tregs to the tumor microenvironment.