Several beneficial effects of metformin on anti-tumor immunity. Metformin indirectly increases T-cell activity by negatively regulating (A) chronic inflammation, (B) hypoxia, and (C) PD-L1 levels that inhibit T-cell activity. (D) Metformin directly relieves T-cell exhaustion by means of metabolic reprogramming of TIL and promotes memory T-cell differentiation. (E) Metformin shifts the profile of gut microbiota more favorably to T-cell immunity (TAM) tumor-associated macrophages; (Mj) macrophages; (MDSC) myeloid-derived suppressor cells; (T) T-cell; (DAMPs) Damage-associated molecular patterns; (APC) antigen presenting; (SCFA) short-chain fatty acid.
