CCR8 is a G protein-coupled chemokine receptor that functions primarily as a marker and mediator of tumor-infiltrating regulatory T cell (TI-Treg) activity. CCR8 is highly and specifically expressed on activated, suppressive TI-Treg cells in multiple human cancers including lung cancer, ovarian cancer, breast cancer, and melanoma, but shows minimal expression on peripheral Tregs 123. CCR8 expression on Tregs is induced through TCR-mediated triggering in an NF-κB-dependent manner 1, and its ligands CCL1, CCL18, and CCL22 facilitate Treg recruitment to tumor microenvironments 45. Mechanistically, CCR8 is not essential for Treg recruitment, activation, or suppressive capacity, but serves as a selective biomarker for the most immunosuppressive TI-Treg subpopulation 1. In cancer immunotherapy, CCR8+ TI-Treg presence correlates with resistance to anti-PD-1 therapy and poor response outcomes 678. Therapeutically, CCR8-targeted depletion using ADCC-prone nanobodies or antibodies selectively eliminates TI-Tregs while sparing peripheral Tregs, enhancing antitumor immunity when combined with anti-PD-1 therapy 1. Beyond cancer, CCR8+ Tregs maintain maternal-fetal tolerance during pregnancy, with decreased CCR8+ Tregs associated with recurrent pregnancy loss 5.