A recent study showed that in vivo hypoglycemia and hypoxia metabolic stress caused CD8+ T cell exhaustion (which was independent of the PD-1 pathway however); fatty acid catabolism enhanced in CD8+ T cells (which was also observed in melanoma patients) partially preserved antitumor effector functions of CD8+ TILs but upregulated (possibly indirectly) PD-1 expression; PD-1 blockade synergizes (but did not change) this metabolic reprogramming in inhibiting tumor growth (28). The gene discussed is CD8A; the disease is melanoma.