CD8+ T cells in the cancer-immunity cycle

• Published in: Immunity (Cambridge, Mass.) Mass.), 2023-10, Vol.56 (10), p.2231-2253
• Main Authors: Giles, Josephine R., Globig, Anna-Maria, Kaech, Susan M., Wherry, E. John
• Format: Article
• Language: English
• Subjects: cancer; CD8 T cells; CD8-Positive T-Lymphocytes; Humans; immune checkpoint blockade; immunology; Immunotherapy; Lymphocyte Activation; metabolism; Neoplasms; T cell exhaustion; Tumor Microenvironment
• ISSN: 1074-7613; 1097-4180; 1097-4180
• 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 cells are “end effectors” of cancer immunity. Wherry, Kaech, and colleagues review the current understanding of CD8+ T cell differentiation and function in cancer, discussing recent advances within a four-signal framework that incorporates T cell metabolism and the impact of the tumor microenvironment.