Age-associated remodeling of T cell immunity and metabolism

SeongJun Han; Peter Georgiev; Alison E Ringel; Arlene H Sharpe; Marcia C Haigis

doi:10.1016/j.cmet.2022.11.005

Age-associated remodeling of T cell immunity and metabolism

Cell Metab. 2023 Jan 3;35(1):36-55. doi: 10.1016/j.cmet.2022.11.005. Epub 2022 Dec 5.

Authors

SeongJun Han¹, Peter Georgiev¹, Alison E Ringel², Arlene H Sharpe³, Marcia C Haigis⁴

Affiliations

¹ Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
² Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: arlene_sharpe@hms.harvard.edu.
⁴ Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: marcia_haigis@hms.harvard.edu.

Abstract

Aging results in remodeling of T cell immunity and is associated with poor clinical outcomes in age-related diseases such as cancer. Among the hallmarks of aging, changes in host and cellular metabolism critically affect the development, maintenance, and function of T cells. Although metabolic perturbations impact anti-tumor T cell responses, the link between age-associated metabolic dysfunction and anti-tumor immunity remains unclear. In this review, we summarize recent advances in our understanding of aged T cell metabolism, with a focus on the bioenergetic and immunologic features of T cell subsets unique to the aging process. We also survey insights into mechanisms of metabolic T cell dysfunction in aging and discuss the impacts of aging on the efficacy of cancer immunotherapy. As the average life expectancy continues to increase, understanding the interplay between age-related metabolic reprogramming and maladaptive T cell immunity will be instrumental for the development of therapeutic strategies for older patients.

Keywords: T cells; aging; cancer; immunity; immunotherapy; metabolism; mitochondria.

Publication types

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

MeSH terms

Aged
Energy Metabolism
Humans
Immunotherapy / methods
Neoplasms* / pathology
T-Lymphocyte Subsets* / metabolism
Tumor Microenvironment

Abstract

Publication types

MeSH terms

Grants and funding