Effects of PD-1 Signaling on Immunometabolic Reprogramming

Programmed Death-1 (PD-1; CD279) is an inhibitory receptor induced in several activated immune cells and, after engagement with its ligands PD-L1 and PD-L2, serves as a key mediator of peripheral tolerance. However, PD-1 signaling also has detrimental effects on T cell function by posing breaks on antitumor and antiviral immunity. PD-1 blocking immunotherapy either alone or in combination with other therapeutic modalities has shown great promise in cancer treatment. However, it is unclear why only a small fraction of patients responds to this type of therapy. For this reason, efforts to better understand the mechanisms of PD-1 function have recently been intensified, with the goal to reveal new strategies to overcome current limitations. The signaling pathways that are inhibited by PD-1 impact key regulators of metabolism. Here, we provide an overview of the current knowledge about the effects of PD-1 on metabolic reprogramming of immune cells and their consequences on systemic metabolism.