4.6 Article

Metabolic interventions: A new insight into the cancer immunotherapy

Journal

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 697, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2020.108659

Keywords

Metabolic reprogramming; Nutrients competing; Tumor microenvironment; Tumor-infiltrating lymphocytes; Immunometabolism

Funding

  1. US National Institutes of Health [R01CA203737, R01CA222251, T32GM077229]
  2. US Department of Defense Prostate Cancer Research Program Idea Development Award [PC190042]
  3. Indiana University Strategic Research Initiative fund
  4. Vera Bradley Foundation for Breast Cancer Research

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Metabolic reprogramming is a key factor in the competition between cancer cells and immune cells in the tumor microenvironment. Therapeutic strategies targeting the metabolic dependence of cancer cells can restore anti-tumor responses of T cells.
Metabolic reprogramming confers cancer cells plasticity and viability under harsh conditions. Such active alterations lead to cell metabolic dependency, which can be exploited as an attractive target in development of effective antitumor therapies. Similar to cancer cells, activated T cells also execute global metabolic reprogramming for their proliferation and effector functions when recruited to the tumor microenvironment (TME). However, the high metabolic activity of rapidly proliferating cancer cells can compete for nutrients with immune cells in the TME, and consequently, suppressing their anti-tumor functions. Thus, therapeutic strategies could aim to restore T cell metabolism and anti-tumor responses in the TME by targeting the metabolic dependence of cancer cells. In this review, we highlight current research progress on metabolic reprogramming and the interplay between cancer cells and immune cells. We also discuss potential therapeutic intervention strategies for targeting metabolic pathways to improve cancer immunotherapy efficacy.

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