Although metformin is likely to work synergistically with ICIs by modulating metabolic pathways of tumor cells and immune cells, the observed benefits may also contribute to its ability to not only inhibit the tolerogenic M2-TAMs [165], plausibly via modifying their lipid metabolism and kynurenine metabolic pathway [166,167], but also enhance PD-L1 degradation [168]. This evidence concerns the gene CD274 and neoplasm.