Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1)

Nerea Allende-Vega; Joaquin Marco Brualla; Paolo Falvo; Catherine Alexia; Michael Constantinides; Alexis Fayd-Herbe-de-Maudave; lois coenon; delphine gitenay; Giulia Mitola; paul massa; stefania orecchioni; Francesco Bertolini; Isabel Marzo; Alberto Anel; Martin Villalba

doi:10.20944/preprints202107.0484.v1

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preprints.org > medicine and pharmacology > immunology and allergy > doi: 10.20944/preprints202107.0484.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1)

Nerea Allende-Vega

Joaquin Marco Brualla

Paolo Falvo

Catherine Alexia

Michael Constantinides

Alexis Fayd-Herbe-de-Maudave

^* ,

Version 1 : Received: 19 July 2021 / Approved: 21 July 2021 / Online: 21 July 2021 (10:54:14 CEST)

How to cite: Allende-Vega, N.; Marco Brualla, J.; Falvo, P.; Alexia, C.; Constantinides, M.; Fayd-Herbe-de-Maudave, A.; coenon, L.; gitenay, D.; Mitola, G.; massa, P.; orecchioni, S.; Bertolini, F.; Marzo, I.; Anel, A.; Villalba, M. Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1). Preprints 2021, 2021070484. https://doi.org/10.20944/preprints202107.0484.v1 Allende-Vega, N.; Marco Brualla, J.; Falvo, P.; Alexia, C.; Constantinides, M.; Fayd-Herbe-de-Maudave, A.; coenon, L.; gitenay, D.; Mitola, G.; massa, P.; orecchioni, S.; Bertolini, F.; Marzo, I.; Anel, A.; Villalba, M. Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1). Preprints 2021, 2021070484. https://doi.org/10.20944/preprints202107.0484.v1

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MDPI and ACS Style

Allende-Vega, N.; Marco Brualla, J.; Falvo, P.; Alexia, C.; Constantinides, M.; Fayd-Herbe-de-Maudave, A.; coenon, L.; gitenay, D.; Mitola, G.; massa, P.; orecchioni, S.; Bertolini, F.; Marzo, I.; Anel, A.; Villalba, M. Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1). Preprints 2021, 2021070484. https://doi.org/10.20944/preprints202107.0484.v1

APA Style

Allende-Vega, N., Marco Brualla, J., Falvo, P., Alexia, C., Constantinides, M., Fayd-Herbe-de-Maudave, A., coenon, L., gitenay, D., Mitola, G., massa, P., orecchioni, S., Bertolini, F., Marzo, I., Anel, A., & Villalba, M. (2021). Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1). Preprints. https://doi.org/10.20944/preprints202107.0484.v1

Chicago/Turabian Style

Allende-Vega, N., Alberto Anel and Martin Villalba. 2021 "Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1)" Preprints. https://doi.org/10.20944/preprints202107.0484.v1

Abstract

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

Keywords

metformin; Natural Killer cells; Cytotoxic T lymphocytes; intercellular adhesion molecule-1 (ICAM-1); Natural Killer G2-D (NKG2D) ligands (NKG2DL); lymphocyte function-associated antigen 1 (LFA-1)

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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