Metabolic programs tailor T cell immunity in viral infection, cancer, and aging

Productive T cell responses to infection and cancer rely on coordinated metabolic reprogramming and epigenetic remodeling among the immune cells. In particular, T cell effector and memory differentiation, exhaustion, and senescence/aging are tightly regulated by the metabolism-epigenetics axis. In this re-view, we summarize recent advances of how metabolic circuits combined with epigenetic changes dictate T cell fate decisions and shape their functional states. We also discuss how the metabolic-epige-netic axis orchestrates T cell exhaustion and explore how physiological factors, such as diet, gut micro-biota, and the circadian clock, are integrated in shaping T cell epigenetic modifications and functionality. Furthermore, we summarize key features of the senescent/aged T cells and discuss how to ameliorate vaccination-and COVID-induced T cell dysfunctions by metabolic modulations. An in-depth understand-ing of the unexplored links between cellular metabolism and epigenetic modifications in various physio-logical or pathological contexts has the potential to uncover novel therapeutic strategies for fine-tuning T cell immunity.

Automated summary

This review summarizes recent advances in understanding the role of metabolism and epigenetics in determining the fate and function of T cells, and discusses strategies for improving T cell dysfunction through metabolic and epigenetic modulation.