Metformin as a booster of cancer immunotherapy

Metformin, a biguanide antidiabetic, has been studied for its repurposing effects in oncology. Although a modest effect was observed in a single-agent regimen, metformin can synergize the anti-tumor effects of other modalities. The promising combination for cancer treatment is with immunotherapy. Despite high efficacy for some cancers, immunotherapy could be limited by modulation of the tumor immune microenvironment and the immune exhaustion of cytotoxic immune cells. Combining immunotherapy with metformin, thus, exerted a rescuing effect of immunotherapy and potentiated the anti-tumor effects of each other. Although not fully understood, metformin shows promoting effects of immunotherapy by several mechanisms. Those proposed mechanisms have been partially proven and are suggested for possible therapeutic strategies for cancer treatment. In this review, a state-of-the-art of metformin's boosting effects on immunotherapy is reviewed and discussed. The future directions for metformin research in preclinical and clinical immunotherapy are also suggested.