Mitochondria determine response to anti-programmed cell death protein-1 (anti-PD-1) immunotherapy: An evidence-based hypothesis

•Studies have yet to define predictive biomarkers of anti-PD-1 therapy.•Epidemiological studies signal mitochondrial effect on anti-PD-1 therapy.•Mitotoxic factors are associated with PD-1 overexpression on T cells.•Mitochondrial boosters reduce PD-1 expression on T cells.•Enhanced mitochondria improve prognosis to anti-PD-1 therapy. Immunotherapy based on programmed cell death protein-1 (PD-1) is a promising approach in oncology. However, a significant fraction of patients remain unresponsive. Therefore, it is imperative to clarify the relevant predictive factors. A decrease in cellular adenosine triphosphate (c-ATP) level can predispose to cellular dysfunction. ATP is a prerequisite for proper T cell migration and activation. Therefore, a decrease in the c-ATP level impairs T cell function and promotes cancer progression. This article gives an overview of the potential predictive factors of PD-1 blockade. Besides, it highlights the pivotal role of mitochondria in response to anti-PD-1 therapies.