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

Autor: Martin Villalba, Francesco Bertolini, Joaquin Marco Brualla, Paolo Falvo, Catherine Alexia, Alexis Fayd'herbe de Maudave, Paul Massa, Stefania Orecchioni, Nerea Allende-Vega, Lois Coenon, Delphine Gitenay, Michael Constantinides, Isabel Marzo, Alberto Anel, Giulia Mitola
Přispěvatelé: KARLI, Mélanie, Laboratoires d'excellence - Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used - - MAbImprove2010 - ANR-10-LABX-0053 - LABX - VALID, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Zaragoza - Universidad de Zaragoza [Zaragoza], European Institute of Oncology [Milan] (ESMO), Institut Sainte Catherine [Avignon], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), This work was supported by the PRT-K program 2018 and 2021(MV, 2018-021). This work was also supported by the 'Investissements d’avenir' Grant LabEx MAbImprove: ANR-10-LABX-53 (MV), the NK 001 project fnanced by the 'Fond Européen de Développement Régional ' (FEDER-FSE-IEJ 2014/2020) and by 'Région Occitanie Pyrénées-Méditerranée', by grant PID2019-105128RB-I00 from Ministerio de Ciencia e Innovación to AA and by Gobierno de Aragón (Group B31_20R) cofnanced by Feder 2014–2020 'Building Europe from Aragon' and Grants from AIRC and Italian Ministry of Health (FB)., ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010)
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports
Scientific Reports, Vol 12, Iss 1, Pp 1-12 (2022)
Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname
Scientific Reports, Nature Publishing Group, 2022, 12 (1), pp.1341. ⟨10.1038/s41598-022-05470-x⟩
ISSN: 2045-2322
DOI: 10.21203/rs.3.rs-830815/v2
Popis: 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.
Databáze: OpenAIRE
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