Figure 4.

Metabolic reprogramming of terminally exhausted T cells. Different strategies could be used to specifically target the metabolism and the mitochondrial fitness of terminally exhausted T cells. The deletion of mitochondrial regulator REGNASE‐1 can increase mitochondrial quality in a BATF‐dependent manner. Preserving mitochondrial health against the accumulation of mitochondrial ROS by N‐acetylcysteine can also restore T‐cell effector function and memory‐like phenotype. Mitochondrial fusion and biogenesis can be rescued through p38‐MAPK and PGC1‐α activation by 4‐1BB stimulation. Treatment with IL‐10‐Fc fusion protein was able reprogram the metabolism of terminally exhausted TILs by promoting oxidative phosphorylation by the mitochondrial pyruvate carrier MPC.