Metformin impacts the differentiation of mouse bone marrow cells into macrophages affecting tumour immunity

Background: Epidemiological studies suggest that metformin reduces the risk of developing several types of cancer, including gliomas, and improves the overall survival in cancer patients. Nevertheless, while the effect of metformin on cancer cells has been extensively studied, its impact on other components of the tumour microenvironment, such as macrophages, is less understood. Results: Metformin-treated mouse bone marrow cells differentiate into spindle-shaped macrophages exhibiting increased phagocytic activity and tumour cell cytotoxicity coupled with modulated expression of co-stimulatory molecules displaying reduced sensitivity to inflammatory cues compared with untreated cells. Transcriptional analyses of metformin-treated mouse bone marrow-derived macrophages show decreased expression levels of pro-tumour genes, including Tgfbi and Il1 beta, related to enhanced mTOR/HIF1 alpha signalling and metabolic rewiring towards glycolysis. Significance: Our study provides novel insights into the immunomodulatory properties of metformin in macrophages and its potential application in preventing tumour onset and in cancer immunotherapy.