Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy

Cell Metab. 2017 Jul 5;26(1):94-109. doi: 10.1016/j.cmet.2017.06.016.


Cancer immunotherapy is an increasingly successful strategy for the treatment of patients who have advanced or conventional therapy-resistant cancers. T cells are key mediators of tumor destruction and their specificity for tumor-expressed antigens is of paramount importance, but other T cell-intrinsic qualities, such as durability, longevity, and functionality also play important roles in determining the efficacy of immunotherapy. The cellular energetic pathways that are utilized by T cells play a key role in regulating each of these qualities. Metabolic activity, which both regulates and is regulated by cellular signaling pathways and epigenetics, also profoundly influences the trajectories of T cell differentiation and fate. In this Review, we discuss how cell metabolism influences T cell anti-tumor activity, the metabolic qualities of highly-functional T cells, and strategies to modulate metabolism for improving the immune response to tumors.

Keywords: T cell metabolism; aging; cancer; checkpoint inhibitor; differentiation; epigenetics; immunotherapy; longevity; memory; tumor.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Survival
  • Epigenesis, Genetic
  • Humans
  • Immunity, Cellular
  • Immunotherapy / methods*
  • Metabolic Networks and Pathways*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Neoplasms / therapy*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Tumor Microenvironment