Emerging role of metabolic reprogramming in tumor immune evasion and immunotherapy

Sci China Life Sci. 2021 Apr;64(4):534-547. doi: 10.1007/s11427-019-1735-4. Epub 2020 Aug 17.

Abstract

Mounting evidence has revealed that the therapeutic efficacy of immunotherapies is restricted to a small portion of cancer patients. A deeper understanding of how metabolic reprogramming in the tumor microenvironment (TME) regulates immunity remains a major challenge to tumor eradication. It has been suggested that metabolic reprogramming in the TME may affect metabolism in immune cells and subsequently suppress immune function. Tumor cells compete with infiltrating immune cells for nutrients and metabolites. Notably, the immunosuppressive TME is characterized by catabolic and anabolic processes that are critical for immune cell function, and elevated inhibitory signals may favor cancer immune evasion. The major energy sources that supply different immune cell subtypes also undergo reprogramming. We herein summarize the metabolic remodeling in tumor cells and different immune cell subtypes and the latest advances underlying the use of metabolic checkpoints in antitumor immunotherapies. In this context, targeting both tumor and immune cell metabolic reprogramming may enhance therapeutic efficacy.

Keywords: antitumor immunotherapy; infiltrating immune cells; metabolic reprogramming; tumor immune evasion; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cellular Reprogramming / drug effects*
  • Cellular Reprogramming / immunology
  • Energy Metabolism / drug effects*
  • Energy Metabolism / immunology
  • Humans
  • Immunotherapy / methods*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Tumor Escape / drug effects*
  • Tumor Escape / immunology
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / immunology
  • Tumor-Associated Macrophages / drug effects
  • Tumor-Associated Macrophages / immunology
  • Tumor-Associated Macrophages / metabolism

Substances

  • Antineoplastic Agents