Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Immunity. 2023 Oct 10;56(10):2231-2253. doi: 10.1016/j.immuni.2023.09.005.
CD8 T cells are end effectors of cancer immunity. Most forms of effective cancer immunotherapy involve CD8 T cell effector function. Here, we review the current understanding of T cell function in cancer, focusing on key CD8 T cell subtypes and states. We discuss factors that influence CD8 T cell differentiation and function in cancer through a framework that incorporates the classic three-signal model and a fourth signal-metabolism-and also consider the impact of the tumor microenvironment from a T cell perspective. We argue for the notion of immunotherapies as "pro-drugs" that act to augment or modulate T cells, which ultimately serve as the drug in vivo, and for the importance of overall immune health in cancer treatment and prevention. The progress in understanding T cell function in cancer has and will continue to improve harnessing of the immune system across broader tumor types to benefit more patients.
CD8 T 细胞是癌症免疫的效应细胞。大多数有效的癌症免疫疗法都涉及 CD8 T 细胞效应功能。在这里，我们综述了对癌症中 T 细胞功能的现有理解，重点关注关键的 CD8 T 细胞亚群和状态。我们通过整合经典三信号模型和第四信号代谢的框架讨论了影响癌症中 CD8 T 细胞分化和功能的因素，并从 T 细胞的角度考虑了肿瘤微环境的影响。我们认为免疫疗法是“前药”，可以增强或调节 T 细胞，而 T 细胞最终在体内发挥作用，并且整体免疫健康对于癌症治疗和预防很重要。对癌症中 T 细胞功能的理解的进展已经并将继续改善对免疫系统的广泛利用，以造福更多的患者。
