Cryo-EM structure of CCR8 receptor

CCR8 is a chemokine receptor that is expressed principally on regulatory T cells (Treg). Tregs suppress the host immune response and maintain immune homeostasis. Tregs in tumor microenvironment promote cancer progression and are involved in resistance to immune checkpoint inhibitor treatments. Recent studies have demonstrated that CCR8 is selectively expressed in human tumor-resident Tregs and its expression is critical for CCR8 + Treg-mediated immunosuppression. CCR8 have been identified as a new theraeputic target of cancer immunotherapy and anti-CCR8 monoclonal antibodies have been developed for cancer treatment. The structures of CCR8 alone and its complex with monoclonal antibodies will provide valuable information for the development of therapeutic anti-CCR8 antibodies. So far no three dimensional structure of CCR8 is available, due to the difficulty in expression and purification of this receptor, and the small size of CCR8 is also a challenge for cryo-EM studies. We have developed a noval fusion-protein approach to overcome the challenges, and solved the cryo-EM structure of CCR8 in apo state at a resolution of 3.24Å.