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Regulatory T Cell Metabolism in Cancer.

Keywan Mortezaee1,2

  • 1Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Immunology
|December 28, 2025
PubMed
Summary
This summary is machine-generated.

Regulatory T cells (Tregs) adapt to the tumor microenvironment (TME) through metabolic pathways like glycolysis and oxidative phosphorylation (OXPHOS). Understanding Treg metabolism offers new cancer immunotherapy targets.

Keywords:
adenosinearyl hydrocarbon receptor (AHR)glycolysishypoxia inducible factor (HIF)lactateliver kinase B1 (LKB1)metforminoxidative phosphorylation (OXPHOS)regulatory T cell (Treg)α‐Ketoglutarate (αKG)

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Area of Science:

  • Immunology
  • Metabolic pathways
  • Cancer biology

Background:

  • Regulatory T cells (Tregs) are crucial for immune suppression within the tumor microenvironment (TME).
  • Tregs utilize metabolic pathways like glycolysis and oxidative phosphorylation (OXPHOS) to survive and function in the TME.
  • The TME's unique conditions (hypoxia, acidity) influence Treg metabolism and anti-tumor immunity.

Purpose of the Study:

  • To review the metabolic regulators and metabolic network (connectome) of Tregs in the TME.
  • To explore how Treg metabolism impacts anti-tumor immunity and metastasis.
  • To identify potential therapeutic targets within Treg metabolism for cancer immunotherapy.

Main Methods:

  • Review of existing literature on Treg metabolism in the TME.
  • Analysis of metabolic pathways including glycolysis, OXPHOS, and lactate metabolism.
  • Discussion of key regulators such as HIF-1, Tfam, LKB1, AMPK, and IDO.

Main Results:

  • Tregs exhibit metabolic plasticity, utilizing glycolysis and OXPHOS to maintain function in the TME.
  • Metabolic byproducts like lactate and succinate play complex roles in Treg activity and TME acidosis.
  • Key regulators like HIF-1, Tfam, LKB1, and AMPK influence Treg stability, function, and immune-suppressive properties.
  • Metabolic interventions (e.g., αKG, metformin) can modulate Treg metabolism.
  • Indoleamine 2,3-dioxygenase (IDO) is highlighted as a potential therapeutic target.

Conclusions:

  • Treg metabolic fitness is essential for immune evasion in the TME.
  • Targeting Treg metabolic pathways presents a promising strategy for enhancing cancer immunotherapy.
  • Further research into the Treg metabolic connectome can uncover novel therapeutic opportunities.