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<p>Regulatory T (T<sub>reg</sub>) cells play critical roles in maintaining immune tolerance and tissue homeostasis, but impede anti-tumor immunity. Recent work has established how T<sub>reg</sub> cells metabolically adapt within the tumor microenvironment (TME), and these adaptations frequently provide a functional advantage over effector T cells. Further, enhanced T<sub>reg</sub> cell function in the TME may contribute to the limited efficacy of current immunotherapies, especially immune checkpoint blockade (ICB). Here, we review recent progress in understanding mechanisms of T<sub>reg</sub> cell heterogeneity and function in tumors, with a particular focus on cellular metabolism as an underlying factor by which T<sub>reg</sub> cells are uniquely poised to thrive in the TME and contribute to tumorigenesis. We describe how cellular metabolism and nutrient or metabolic communication shape T<sub>reg</sub> cell lineage identity and function in the TME. We also discuss the interplay between ICB and T<sub>reg</sub> cell metabolism and function, and highlight current strategies targeting T<sub>reg</sub> cell metabolism specifically in the TME. Understanding metabolic control of intratumoral T<sub>reg</sub> cells provides excellent opportunities to uncover new or combination therapies for cancer.</p>

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Immunometabolism of regulatory T cells in cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月4日

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  • Jordy Saravia,
  • Hongbo Chi

摘要

Regulatory T (Treg) cells play critical roles in maintaining immune tolerance and tissue homeostasis, but impede anti-tumor immunity. Recent work has established how Treg cells metabolically adapt within the tumor microenvironment (TME), and these adaptations frequently provide a functional advantage over effector T cells. Further, enhanced Treg cell function in the TME may contribute to the limited efficacy of current immunotherapies, especially immune checkpoint blockade (ICB). Here, we review recent progress in understanding mechanisms of Treg cell heterogeneity and function in tumors, with a particular focus on cellular metabolism as an underlying factor by which Treg cells are uniquely poised to thrive in the TME and contribute to tumorigenesis. We describe how cellular metabolism and nutrient or metabolic communication shape Treg cell lineage identity and function in the TME. We also discuss the interplay between ICB and Treg cell metabolism and function, and highlight current strategies targeting Treg cell metabolism specifically in the TME. Understanding metabolic control of intratumoral Treg cells provides excellent opportunities to uncover new or combination therapies for cancer.