CD274 and obesity due to melanocortin 4 receptor deficiency: Indeed, the synergistic effect of metformin should be reweighted when considering the apparently paradoxical association between obesity and increased anti-tumor efficacy and survival after PD-1/PD-L1 blockade (as recent evidence suggested a positive correlation between overweight and the efficacy of ICIs, the anticancer effects of metformin might be false-positive results, since metformin is a typical drug used in diabetics who often have characteristics such as overweight or obesity with metabolic disturbances) [190,191].