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.

有效的抗肿瘤免疫是由对肿瘤抗原具有特异性的细胞毒性 CD8⁺ T 细胞驱动的。然而，控制肿瘤排斥反应成功的因素尚不清楚。在这里，我们鉴定了一个 CD8 ⁺ T 细胞亚群，这些细胞是肿瘤抗原特异性的，可以通过 KIR 表达来识别，但矛盾的是会损害黑色素瘤患者的抗肿瘤免疫力。这些肿瘤抗原特异性 KIR⁺CD8⁺ 调节性 T 细胞靶向其他肿瘤抗原特异性 CD8⁺ T 细胞，可以在肿瘤和血液中检测到，具有保守的转录程序，并且与较差的总生存期相关。这些发现拓宽了我们对人 CD8⁺ T 细胞转录和功能异质性的理解，并暗示 KIR⁺CD8⁺ 调节性 T 细胞是人类癌症中免疫逃避的细胞介质。