CCR8 is a chemokine receptor that belongs to the β chemokine receptor family, the single crystal structure has not been deciphered, but is predicted to be a seven-transmembrane protein, similar to G-protein-coupled receptors. CCR8 expression is low or absent in Treg of normal tissues (e.g.thymus, spleen) and peripheral blood, predominantly highly expressed in tumor-infiltrating Treg. Chemokines and their receptors are important for the migration of various cell types into the inflammatory sites. In human peripheral blood cells, over 30% of Treg upregulate CCR8 in response to CCL1. This interaction induces stat3-dependent upregulation of FOXp3, CD39, IL-10, and granzyme B, which enhances the immunosuppressive activity of these Treg cells. There are currently four known human CCR8 ligands, CCL1, CCL8, CCL16, and CCL18, of which CCR8 is a specific receptor for CCL1, which has a more significant role in enhancing Treg cell immunosuppression.CCR8 may be an effective therapeutic target by which to selectively and specifically modulate a subpopulation of tumor-resident Tregs in the TME to augment antitumor immunity. CCR8 may be a promising new target for cancer immunotherapy and its potential for broad clinical application.
mRNA expression analysis
Strain specific analysis of CCR8 gene expression in WT and B-hCCR8 mice by RT-PCR. Mouse Ccr8 mRNA was detectable in thymocyte of wild-type (+/+). Human CCR8 mRNA was detectable in B-hCCR8 mice (H/H) mice but not in wild-type mice.
Protein expression analysis
Strain specific analysis of CCR8 gene expression in B-hCCR8 mice by FACS. MC38 cells(1×10^6) were Inoculated into WT and B-hCCR8(H/H) mice. Tumors were harvested at the endpoint of experiment, and the TILs were analyzed by flow cytometry. Human CCR8 was detectable on CD4+ T cells and Treg cells in B-hCCR8(H/H) mice, and mouse CCR8 was detectable only in WT mice.