Caloric restriction promotes the stemness and antitumor activity of T lymphocytes

Recent findings have shed new light on the mechanisms through which tumor-infiltrating lymphocytes (TILs) maintain their cytotoxic potential in the context of checkpoint blockade or adoptive transfer therapies. As a consequence of the ionic unbalance occurring in the tumor microenvironment, TILs enter an adaptive caloric-restricted state, characterized by a decline in nucleocytosolic acetyl CoA levels and induction of autophagy. These events dictate an epigenetic program that drives the acquisition of a stem-cell-like phenotype and ultimately improves antitumor function. These findings open the way to novel anticancer therapies based on the induction of autophagy by pharmacological caloric restriction mimetics.