Emerging concepts of T cell metabolism as a target of immunotherapy

Nat Immunol. 2016 Apr;17(4):364-8. doi: 10.1038/ni.3415.

Abstract

T cells have a pivotal protective role in defense against infection and cancer but also are instrumental in the development of many autoimmune diseases. The regulation of nutrient uptake and utilization in T cells is critically important for the control of their differentiation, and manipulating metabolic pathways in these cells can alter their function and longevity. While the importance of T cell metabolic remodeling in different physiological settings is not fully understood, there is a growing realization that inappropriate metabolic remodeling underlies many aberrant immune responses and that manipulating cellular metabolism can beneficially enhance or temper immunity. Here we comment on the basic metabolic pathways in T cells, followed by a discussion on up-to-date findings about the relationship between metabolism and T cell function and longevity. Furthermore, we expand on potential approaches and applications in which T cells might be manipulated by the reprogramming of metabolic pathways for therapeutic purposes.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism
  • Cell Differentiation / immunology
  • Glycolysis
  • Humans
  • Immunotherapy
  • Immunotherapy, Adoptive*
  • Metabolic Networks and Pathways
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Oxidative Phosphorylation
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Microenvironment / immunology

Substances

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