Mitochondria orchestrate T cell fate and function

Abstract

An investigation of the molecular processes of mitochondrial reprogramming and metabolic stress in antigen-experienced T cells within tumor microenvironments reveals mechanisms responsible for T cell exhaustion and dysfunction and facilitates the development of new strategies for tumor immunotherapy.

Fig. 1 |. Mitochondrial reprogramming for the development of exhausted T cells within the tumor microenvironment.

Multiple tumor microenvironmental factors are involved in the development of exhaustion in T cells within tumors, including glucose competition and metabolite accumulation, chronic tumor antigenic stimulation through the TcR, hypoxia and PD-1–PD-L1 signaling. These immunologic and metabolic factors decrease the quantity and alter the functions and activities of mitochondria, which promote the epigenetic, transcriptional and metabolic reprogramming of T cells. Mitochondria orchestrate these molecular processes and drive the development of terminally exhausted T cells in the tumor microenvironment.