Lu Benjamin Y, Lucca Liliana E, Lewis Wesley, Wang Jiping, Nogueira Catarina V, Heer Sebastian, Rayon-Estrada Violeta, Axisa Pierre-Paul, Reeves Sarah M, Buitrago-Pocasangre Nicholas C, Pham Giang H, Kojima Mina L, Wei Wei, Aizenbud Lilach, Bacchiocchi Antonietta, Zhang Lin, Walewski Joseph J, Chiang Veronica, Olino Kelly, Clune James, Halaban Ruth, Kluger Yuval, Coyle Anthony J, Kisielow Jan, Obermair Franz-Josef, Kluger Harriet M, Hafler David A
Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, CT, USA.
Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Nat Immunol. 2025 Jan;26(1):82-91. doi: 10.1038/s41590-024-02023-4. Epub 2024 Nov 28.
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 KIRCD8 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 KIRCD8 regulatory T cells as a cellular mediator of immune evasion in human cancer.
有效的抗肿瘤免疫由对肿瘤抗原具有特异性的细胞毒性CD8 T细胞驱动。然而，控制肿瘤成功排斥的因素尚未完全明确。在此，我们鉴定出一类CD8 T细胞亚群，它们对肿瘤抗原具有特异性，可通过KIR表达来识别，但矛盾的是，它们会损害黑色素瘤患者的抗肿瘤免疫。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，可在肿瘤组织和血液中检测到，具有保守的转录程序，并且与总体生存率低相关。这些发现拓宽了我们对人类CD8 T细胞转录和功能异质性的理解，并表明KIR⁺CD8调节性T细胞是人类癌症中免疫逃逸的细胞介质。
