Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes

Immunology. 2017 Oct;152(2):175-184. doi: 10.1111/imm.12777. Epub 2017 Jul 10.

Abstract

Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and up-regulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system. Immune checkpoint blockade provides an example of how metabolism can be differentially impacted to impair cancer cells but support T cells. Implications for research with metabolic inhibitors are discussed.

Keywords: T cells; cancer; tumour immunology.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Proliferation
  • Cellular Reprogramming* / drug effects
  • Energy Metabolism* / drug effects
  • Glycolysis
  • Humans
  • Hydrogen-Ion Concentration
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Oxidative Phosphorylation
  • Phenotype
  • Signal Transduction
  • Tumor Escape
  • Tumor Microenvironment*

Substances

  • Antineoplastic Agents