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T cell InaDAGquacy in the TME driven by phosphoethanolamine

Erica G Brown1, Roddy S O'Connor1

  • 1Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

Developmental Cell
|July 22, 2025
PubMed

Insights

Phosphoethanolamine is an onco-metabolite that impairs T cell function by depleting diacylglycerol. This finding reveals how tumor microenvironment metabolites impact T cell activity.

Area of Science:

  • Immunology
  • Metabolomics
  • Cancer Biology

Background:

  • Tumor microenvironment (TME) metabolites significantly influence immune cell function.
  • T cell-mediated immunity is crucial for anti-tumor responses.
  • Dysregulation of metabolic pathways can impact immune cell activity.

Purpose of the Study:

  • To identify specific metabolites within the TME that affect T cell function.
  • To elucidate the mechanism by which these metabolites disrupt T cell activity.

Main Methods:

  • Metabolomic analysis of the tumor microenvironment.
  • Assays to measure T cell function and viability.
  • Biochemical pathway analysis to understand metabolite-T cell interactions.

Main Results:

  • Phosphoethanolamine was identified as a key onco-metabolite.
  • Phosphoethanolamine disrupts T cell function by depleting diacylglycerol.
  • Diacylglycerol depletion occurs via interference with the Kennedy cycle.

Conclusions:

  • Phosphoethanolamine acts as an onco-metabolite, suppressing T cell function.
  • Metabolites in the TME play a critical role in modulating anti-tumor immunity.
  • Targeting onco-metabolite pathways may offer novel cancer immunotherapy strategies.

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