CCR8 is reported as an important chemokine receptor expressed on intra-tumoral Tregs and plays a critical role in CCR8+ Treg-mediated immunosuppression via inducing STAT3-dependent overexpression of FOXP3, CD39, IL-10, and granzyme B on Tregs with interaction of CCL1 (CCR8 ligand). CCR8 becomes a promising target in the anticancer drug development. Generation of humanized CCR8 mouse model can greatly improve translation and accelerate CCR8-related drug development.