Regulatory T cells (Tregs) are essential to the negative regulation of the immune system, as they avoid excessive
inflammation and mediate
tumor development. The abundance of Tregs in
tumor tissues suggests that Tregs may be eliminated or functionally inhibited to stimulate antitumor immunity. However,
immunotherapy targeting Tregs has been severely hampered by
autoimmune diseases due to the systemic elimination of Tregs. Recently, emerging studies have shown that metabolic regulation can specifically target
tumor-infiltrating immune cells, and
lipid accumulation in TME is associated with immunosuppression. Nevertheless, how Tregs actively regulate metabolic reprogramming to outcompete effector T cells (Teffs), and how
lipid metabolic reprogramming contributes to the immunomodulatory capacity of Tregs have not been fully discussed. This review will discuss the physiological processes by which
lipid accumulation confers a metabolic advantage to
tumor-infiltrating Tregs (TI-Tregs) and amplifies their immunosuppressive functions. Furthermore, we will provide a summary of the driving effects of various metabolic regulators on the metabolic reprogramming of Tregs. Finally, we propose that targeting the lipid metabolism of TI-Tregs could be efficacious either alone or in conjunction with immune checkpoint
therapy.