美国耶鲁大学David A. Hafler等研究人员合作发现，循环肿瘤反应性KIR⁺CD8⁺ T细胞在黑色素瘤患者中抑制抗肿瘤免疫。相关论文于2024年11月28日在线发表在《自然—免疫学》杂志上。

研究人员发现了一种亚群的CD8⁺ T细胞，这些细胞特异性识别肿瘤抗原，并可通过KIR表达进行鉴定，但却悖论性地在黑色素瘤患者中抑制抗肿瘤免疫。

这些肿瘤抗原特异性的KIR⁺CD8⁺调节性T细胞，以肿瘤抗原特异性的CD8⁺ T细胞为靶标，既可在肿瘤组织中检测到，也可在血液中发现，具有保守的转录程序，并与较差的总生存期相关。

这些发现拓宽了人们对人类CD8⁺ T细胞转录和功能异质性的理解，并提示KIR⁺CD8⁺调节性T细胞作为人类癌症免疫逃逸的细胞介导者。

据了解，有效的抗肿瘤免疫由特异性识别肿瘤抗原的，细胞毒性CD8⁺ T细胞驱动。然而，控制成功肿瘤排斥的因素尚不完全明了。

附：英文原文

Title: Circulating tumor-reactive KIR+CD8+ Tcells suppress anti-tumor immunity in patients with melanoma

Author: 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.

Issue&Volume: 2024-11-28

Abstract: Effective anti-tumor immunity is driven by cytotoxic CD8+ Tcells with specificity for tumor antigens. However, the factors that control successful tumor rejection are not well understood. Here we identify a subpopulation of CD8+ Tcells 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+ Tcells, 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.

DOI: 10.1038/s41590-024-02023-4

Source: https://www.nature.com/articles/s41590-024-02023-4