PDCD1 and melanoma: In the same study by Zhang et al. (145) that found a synergistic effect of PD-1 blockade with fatty acid catabolism in a melanoma model, hypoxia-driven hypofunction in CD8+ TILs was accompanied by lower PD-1 expression (but increased LAG-3 expression), and increased PD-1 signaling was hypothesized to be associated with metabolic reprogramming from glycolysis to FAO in low glucose environments like the TME.