@article{e3b1cbc7b78d4ba1bf26f2527d6269cf,
title = "Metformin impacts the differentiation of mouse bone marrow cells into macrophages affecting tumour immunity",
abstract = "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 Il1β, related to enhanced mTOR/HIF1α 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.",
keywords = "Anti-tumour, Glycolysis, HIF1α, Macrophages, Metformin, Phagocytosis",
author = "Andrea Scafidi and {Lind-Holm Mogensen}, Frida and Eleonora Campus and Alexandros Pailas and Katrin Neumann and Nathalie Legrave and Fran{\c c}ois Bernardin and Pereira, {Sandro L.} and Antony, {Paul M.A.} and Nathalie Nicot and Michel Mittelbronn and Anne Gr{\"u}newald and Nazarov, {Petr V.} and Aur{\'e}lie Poli and {Van Dyck}, Eric and Alessandro Michelucci",
note = "Acknowledgments We acknowledge Dr Bjorn Becker for the scientific insights about metabolic reprogramming and mitochondrial dynamics, Ms. Stephanie Sallai and Dr Djalil Coowar for the technical support with the collection of mouse samples, and Mr. Pol Hoffmann for his support with Clariom{\texttrademark} S microarray analyses. We acknowledge financial support from the Action LIONS « Vaincre le Cancer » Luxembourg. FL-HM and EC were supported by the Luxembourg National Research Fund (FNR) through the FNR-PRIDE programs for doctoral education i2TRON (PRIDE/14254520/I2TRON) and CANBIO2 (PRIDE21/16763386/CANBIO2), respectively. MM would like to thank the FNR for the support (FNR PEARL P16/BM/11192868 grant). AG was supported by the FNR within the framework of the ATTRACT program (FNR9631103). PVN was supported by FNR grant (C21/BM/15739125/DIOMEDES). For the purpose of open access, and in fulfilment of the obligations arising from the FNR grant agreement, the author has applied a Creative Commons Attribution 4.0 International (CC BY 4.0) license to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: {\textcopyright} 2024 The Authors",
year = "2024",
month = sep,
day = "30",
doi = "10.1016/j.heliyon.2024.e37792",
language = "English",
volume = "10",
journal = "Heliyon",
issn = "2405-8440",
publisher = "Elsevier BV",
number = "18",
}