Circulating Tumor Reactive KIR+CD8+ T cells Suppress Anti-Tumor Immunity in Patients with Melanoma

Abstract Effective anti-tumor immunity is largely driven by cytotoxic CD8⁺ T cells that can specifically recognize tumor antigens. However, the factors which ultimately dictate successful tumor rejection remain poorly understood. Here we identify a subpopulation of CD8⁺ T cells which are tumor antigen-specific in patients with melanoma but resemble KIR⁺CD8⁺ T cells with a regulatory function (Tregs). These tumor antigen-specific KIR⁺CD8⁺ T cells are detectable in both the tumor and the blood, and higher levels of this population are associated with worse overall survival. Our findings therefore suggest that KIR⁺CD8⁺ Tregs are tumor antigen-specific but uniquely suppress anti-tumor immunity in patients with melanoma.