Circulating tumor-reactive KIR+CD8+T cells suppress anti-tumor immunity in patients with melanoma

Effective anti-tumor immunity is driven by cytotoxic CD8+T cells with specificity for tumor antigens. However, the factors that control successful tumor rejection are not well understood. Here we identify a subpopulation of CD8+T cells that are tumor-antigen-specific and can be identified by KIR expression but paradoxically impair anti-tumor immunity in patients with melanoma. These tumor-antigen-specific KIR+CD8+regulatory T cells target other tumor-antigen-specific CD8+T cells, can be detected in both the tumor and the blood, have a conserved transcriptional program and are associated with a poor overall survival. These findings broaden our understanding of the transcriptional and functional heterogeneity of human CD8+T cells and implicate KIR+CD8+regulatory T cells as a cellular mediator of immune evasion in human cancer.