CD8+ T cells in the cancer-immunity cycle

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.

Keywords: CD8 T cells; T cell exhaustion; cancer; immune checkpoint blockade; immunology; immunotherapy; metabolism.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes*
  • Humans
  • Immunotherapy
  • Lymphocyte Activation
  • Neoplasms*
  • Tumor Microenvironment