Metformin impacts the differentiation of mouse bone marrow cells into macrophages affecting tumour immunity
Andrea Scafidi,
Frida Lind-Holm Mogensen,
Eleonora Campus,
Alexandros Pailas,
Katrin Neumann,
Nathalie Legrave,
François Bernardin,
Sandro L. Pereira,
Paul M.A. Antony,
Nathalie Nicot,
Michel Mittelbronn,
Anne Grünewald,
Petr V. Nazarov,
Aurélie Poli,
Eric Van Dyck,
Alessandro Michelucci
Affiliations
Andrea Scafidi
Neuro-Immunology Group, Department of Cancer Research, Luxembourg Institute of Health, L-1210 Luxembourg, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg
Frida Lind-Holm Mogensen
Neuro-Immunology Group, Department of Cancer Research, Luxembourg Institute of Health, L-1210 Luxembourg, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg
Eleonora Campus
Neuro-Immunology Group, Department of Cancer Research, Luxembourg Institute of Health, L-1210 Luxembourg, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg
Alexandros Pailas
Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg; DNA Repair and Chemoresistance, Department of Cancer Research, Luxembourg Institute of Health, L-1210 Luxembourg, Luxembourg
Katrin Neumann
DNA Repair and Chemoresistance, Department of Cancer Research, Luxembourg Institute of Health, L-1210 Luxembourg, Luxembourg
Nathalie Legrave
Metabolomics Platform, Department of Cancer Research, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg
François Bernardin
Metabolomics Platform, Department of Cancer Research, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg
Sandro L. Pereira
Molecular and Functional Neurobiology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4362 Esch-sur-Alzette, Luxembourg
Paul M.A. Antony
Bioimaging Platform, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4362 Esch-sur-Alzette, Luxembourg
Nathalie Nicot
LuxGen Genome Center, Luxembourg Institute of Health & Laboratoire National de Santé, L-3555 Dudelange, Luxembourg
Michel Mittelbronn
Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, L-4367 Belvaux, Luxembourg; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4362 Esch-sur-Alzette, Luxembourg; Department of Cancer Research, Luxembourg Institute of Health, L-1210 Luxembourg, Luxembourg; Luxembourg Center of Neuropathology, Laboratoire National de Santé, L-3555 Dudelange, Luxembourg; National Center of Pathology, Laboratoire National de Santé, L-3555 Dudelange, Luxembourg
Anne Grünewald
Molecular and Functional Neurobiology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4362 Esch-sur-Alzette, Luxembourg
Petr V. Nazarov
Bioinformatics and AI unit, Department of Medical Informatics, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg; Multiomics Data Science Group, Department of Cancer Research, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg
Aurélie Poli
Neuro-Immunology Group, Department of Cancer Research, Luxembourg Institute of Health, L-1210 Luxembourg, Luxembourg
Eric Van Dyck
DNA Repair and Chemoresistance, Department of Cancer Research, Luxembourg Institute of Health, L-1210 Luxembourg, Luxembourg
Alessandro Michelucci
Neuro-Immunology Group, Department of Cancer Research, Luxembourg Institute of Health, L-1210 Luxembourg, Luxembourg; Corresponding author.
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.
