Immunometabolism of regulatory T cells in cancer
Jordy Saravia, Hongbo Chi
Abstract
Abstract Regulatory T (T reg ) cells play critical roles in maintaining immune tolerance and tissue homeostasis, but impede anti-tumor immunity. Recent work has established how T reg cells metabolically adapt within the tumor microenvironment (TME), and these adaptations frequently provide a functional advantage over effector T cells. Further, enhanced T reg 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 reg cell heterogeneity and function in tumors, with a particular focus on cellular metabolism as an underlying factor by which T reg 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 reg cell lineage identity and function in the TME. We also discuss the interplay between ICB and T reg cell metabolism and function, and highlight current strategies targeting T reg cell metabolism specifically in the TME. Understanding metabolic control of intratumoral T reg cells provides excellent opportunities to uncover new or combination therapies for cancer.