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Other studies (111–114) suggested that metformin may increase tumor response to ICI through a variety of mechanisms, including upregulation of CD8+ tumor-infiltrating lymphocytes and their function, downregulation of myeloid suppressor cells with immunosuppressive effects, reduction of tumor hypoxia, anti-angiogenic effects and shifting the composition of the patient's gut flora to bacterial strains that may respond better to immunotherapy (107)