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Pharmacological effects on anaplerotic pathways alter the metabolic landscape in the tumor microenvironment, causing

Heiichiro Udono1, Mikako Nishida1

  • 1Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan.

International Immunology
|September 7, 2021
PubMed

Insights

Immuno-metabolism research reveals that targeting cellular metabolism can enhance anti-tumor immunity. Pharmacological agents differentially affect tumor cells and CD8 T cells, impacting cancer immunotherapy strategies.

Area of Science:

  • Immunology
  • Metabolic pathways
  • Cancer immunotherapy

Background:

  • Sustained anti-tumor immunity requires CD8 T lymphocytes (CD8 TILs) to produce cytokines like IFNγ and proliferate.
  • IFNγ production relies on glycolysis, while proliferation needs oxidative phosphorylation (OxPhos).
  • OxPhos depends on mitochondrial function and anaplerosis, the process of replenishing the tricarboxylic acid cycle.

Purpose of the Study:

  • To investigate the impact of pharmacological agents on anaplerotic pathways in tumor cells and CD8 TILs.
  • To understand the opposing metabolic effects of these agents on tumor cells versus anti-tumor immune cells.
  • To explore novel cancer immunotherapy strategies based on immuno-metabolism.

Main Methods:

  • Analysis of immuno-metabolic pathways.
  • Investigating the effects of pharmacological agents on cellular metabolism.
  • Evaluating metabolic regulation in tumor cells and CD8 TILs.

Main Results:

  • Pharmacological agents can down-regulate metabolism in tumor cells.
  • These agents can up-regulate both glycolysis and OxPhos in CD8 TILs, promoting anti-tumor immunity.
  • The opposing effects on anaplerosis in tumor cells and CD8 TILs are complex and unpredictable.

Conclusions:

  • Targeting anaplerosis offers a potential strategy for cancer immunotherapy.
  • Understanding the differential metabolic effects on tumor cells and CD8 TILs is crucial.
  • Further research into immuno-metabolism mechanisms can advance cancer treatment.
Keywords:
immuno-metabolismtumor immunity

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