Metabolic Control of CD8+ T Cell Fate Decisions and Antitumor Immunity

Trends Mol Med. 2018 Jan;24(1):30-48. doi: 10.1016/j.molmed.2017.11.005. Epub 2017 Dec 12.

Abstract

CD8+ T cells are central players in controlling infections and cancer. Longevity, functionality, and metabolic fitness are critical determinants of T cell efficacy in cancer immunotherapy. Tumor-infiltrating CD8+ T cells undergo metabolic 'exhaustion' in the nutrient- and oxygen-deprived tumor microenvironment (TME). Thus, reprograming CD8+ T cell metabolism may provide important therapeutic strategies for cancer treatment. Indeed, the adoptive transfer of memory CD8+ T cells with sustained metabolic fitness may yield better antitumor protection in both mouse models and the clinic. Here, we discuss recent progress on how cellular metabolism is linked to CD8+ T cell fate decisions and on how metabolic intermediates can impact gene expression via modulation of the epigenome. We examine the feasibility of developing potential strategies to improve antitumor immunity through the modulation of T cell metabolic activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation
  • Epigenesis, Genetic
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Organelle Biogenesis
  • Protein Kinases / immunology
  • Protein Kinases / metabolism
  • TOR Serine-Threonine Kinases / immunology
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Microenvironment

Substances

  • Protein Kinases
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinase Kinases