Mini reviewRegulatory T cells as suppressors of anti-tumor immunity: Role of metabolism

- We review the role Treg cells in the field of immunometabolism.
- Treg cells sustain tumor progression through suppression of anti-tumour immunity.
- Metabolism in the tumor microenvironment influences anti-tumor immune response through the modulation of T cell fate decision.
- Emerging strategies for cancer immunotherapy have been designed to boost effector T cell responses via either inhibition or depletion of Treg cells within the tumor.

Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response. Current experimental evidence suggests that tumor-derived metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance. For example, several glycolytic enzymes, deregulated in cancer, contribute to tumor progression independently from their canonical metabolic activity. Indeed, they can control apoptosis, gene expression and activation of specific intracellular pathways, thus suggesting a direct link between metabolic switches and pro-tumorigenic transcriptional programs. Focus of this review is to define the specific metabolic pathways controlling Treg cell immunobiology in the context of anti-tumor immunity and tumor progression.

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