Metformin plays an antitumor role by downregulating inhibitory cells and immune checkpoint molecules while activating protective immune responses in breast cancer.

This study seeks to test the effect of metformin treatment on the outcomes of breast cancer in BALB/c mice bearing 4 T1 breast cancer cells. The survival rate and tumor size of mice were compared, as well as evaluation of the changes of immune cells in spleens and the microenvironment of tumors using flow cytometry and ELISA. Our results demonstrate that metformin prolongs mouse survival. A significant decrease in M2-like macrophages (F4/80+CD206+) was found in mice spleen treated with metformin. The treatment also inhibited monocytic myeloid-derived suppressor cells (M-MDSCs, CD11b+Gr-1+) and regulatory T cells (Tregs, CD4+CD25+Foxp3+). Metformin treatment resulted in an increase in the level of IFN-γ and a decrease in IL-10. Expression of the immune checkpoint molecule PD-1 on T cells was inhibited following treatment. Metformin enhances local antitumor activity in the tumor microenvironment, and our data supports the drug as a candidate for evaluation in the treatment of breast cancer.