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A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro
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NK Cell Metabolism and TGFβ - Implications for Immunotherapy

Karen Slattery1, Clair M Gardiner1

  • 1School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland.

Frontiers in Immunology
|January 11, 2020
PubMed

Insights

Natural killer (NK) cells use cellular metabolism for anti-cancer functions. Transforming growth factor beta (TGFβ) can inhibit NK cell metabolism and function, offering potential therapeutic targets for cancer treatment.

Area of Science:

  • Immunology
  • Cellular Metabolism
  • Cancer Biology

Background:

  • Natural killer (NK) cells are crucial innate lymphocytes for anti-cancer and anti-viral immunity.
  • NK cell function is regulated by various factors, including receptors, cytokines, and environmental cues.
  • Cellular metabolism has emerged as a key regulatory layer influencing immune cell function and dynamics.

Purpose of the Study:

  • To review the current understanding of how Transforming Growth Factor beta (TGFβ) regulates NK cell metabolism.
  • To explore potential molecular mechanisms by which TGFβ influences NK cell metabolic pathways.
  • To identify potential therapeutic strategies targeting TGFβ for enhancing adoptive NK cell therapies in cancer treatment.

Main Methods:

  • Literature review focusing on NK cell metabolism and TGFβ signaling.
  • Analysis of existing data on cytokine regulation of immune cell metabolism.
  • Integration of knowledge on TGFβ's broader effects on cellular metabolic pathways.

Main Results:

  • Pro-inflammatory cytokines activate glycolysis and oxidative phosphorylation (oxphos) in NK cells, supporting anti-cancer functions.
  • TGFβ, an anti-inflammatory cytokine, can suppress NK cell metabolic reprogramming and reduce their functional output.
  • Perturbation of metabolic pathways significantly impacts NK cell effector functions.

Conclusions:

  • TGFβ plays a significant role in modulating NK cell metabolism and function.
  • Understanding TGFβ's regulatory mechanisms in NK cells is critical for developing novel cancer immunotherapies.
  • Targeting TGFβ pathways may offer a promising strategy to enhance the efficacy of adoptive NK cell therapies.
Keywords:
NK cellsTGFβimmunotherapymetabolismmitochondria

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