CD8+ T cells in the cancer-immunity cycle

Josephine R Giles; Anna-Maria Globig; Susan M Kaech; E John Wherry

doi:10.1016/j.immuni.2023.09.005

CD8⁺ T cells in the cancer-immunity cycle

Immunity. 2023 Oct 10;56(10):2231-2253. doi: 10.1016/j.immuni.2023.09.005.

Authors

Josephine R Giles¹, Anna-Maria Globig², Susan M Kaech³, E John Wherry⁴

Affiliations

¹ 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.
² NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
³ NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: skaech@salk.edu.
⁴ 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. Electronic address: wherry@pennmedicine.upenn.edu.

PMID: 37820583
DOI: 10.1016/j.immuni.2023.09.005

Abstract

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

Abstract

Publication types

MeSH terms

Grants and funding