Immunometabolism: A new target for improving cancer immunotherapy

Adv Cancer Res. 2019:143:195-253. doi: 10.1016/bs.acr.2019.03.004. Epub 2019 Apr 17.

Abstract

Fundamental metabolic pathways are essential for mammalian cells to provide energy, precursors for biosynthesis of macromolecules, and reducing power for redox regulation. While dysregulated metabolism (e.g., aerobic glycolysis also known as the Warburg effect) has long been recognized as a hallmark of cancer, recent discoveries of metabolic reprogramming in immune cells during their activation and differentiation have led to an emerging concept of "immunometabolism." Considering the recent success of cancer immunotherapy in the treatment of several cancer types, increasing research efforts are being made to elucidate alterations in metabolic profiles of cancer and immune cells during their interplays in the setting of cancer progression and immunotherapy. In this review, we summarize recent advances in studies of metabolic reprogramming in cancer as well as differentiation and functionality of various immune cells. In particular, we will elaborate how distinct metabolic pathways in the tumor microenvironment cause functional impairment of immune cells and contribute to immune evasion by cancer. Lastly, we highlight the potential of metabolically reprogramming the tumor microenvironment to promote effective and long-lasting antitumor immunity for improved immunotherapeutic outcomes.

Keywords: Antitumor immunity; Cancer immunotherapy; Immune checkpoints; Immunometabolism; Tumor microenvironment.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cellular Reprogramming
  • Energy Metabolism
  • Glycolysis
  • Humans
  • Immune System / drug effects
  • Immune System / immunology*
  • Immune System / metabolism
  • Immunotherapy / methods*
  • Metabolome
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Signal Transduction / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Tumor Microenvironment / immunology*

Substances

  • Antineoplastic Agents