000111659 001__ 111659
000111659 005__ 20240319080949.0
000111659 0247_ $$2doi$$a10.1038/s41598-022-05470-x
000111659 0248_ $$2sideral$$a127814
000111659 037__ $$aART-2022-127814
000111659 041__ $$aeng
000111659 100__ $$aAllende-Vega, Nerea
000111659 245__ $$aMetformin sensitizes leukemic cells to cytotoxic lymphocytes by increasing expression of intercellular adhesion molecule-1 (ICAM-1)
000111659 260__ $$c2022
000111659 5060_ $$aAccess copy available to the general public$$fUnrestricted
000111659 5203_ $$aSolid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The anti-diabetic 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 anti-apoptotic 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.
000111659 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B31-20R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00
000111659 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000111659 590__ $$a4.6$$b2022
000111659 592__ $$a0.973$$b2022
000111659 591__ $$aMULTIDISCIPLINARY SCIENCES$$b22 / 73 = 0.301$$c2022$$dQ2$$eT1
000111659 593__ $$aMultidisciplinary$$c2022$$dQ1
000111659 594__ $$a7.5$$b2022
000111659 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000111659 700__ $$aMarco Brualla, Joaquin
000111659 700__ $$aFalvo, Paolo
000111659 700__ $$aAlexia, Catherine
000111659 700__ $$aConstantinides, Michael
000111659 700__ $$aMaudave, Alexis Fayd’herbe de
000111659 700__ $$aCoenon, Lois
000111659 700__ $$aGitenay, Delphine
000111659 700__ $$aMitola, Giulia
000111659 700__ $$aMassa, Paul
000111659 700__ $$aOrecchioni, Stefania
000111659 700__ $$aBertolini, Francesco
000111659 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, Isabel$$uUniversidad de Zaragoza
000111659 700__ $$aAnel, Alberto
000111659 700__ $$aVillalba, Martin
000111659 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000111659 773__ $$g12, 1 (2022), 1341 [12 pp.]$$pSci. rep. (Nat. Publ. Group)$$tScientific reports (Nature Publishing Group)$$x2045-2322
000111659 8564_ $$s1292135$$uhttps://zaguan.unizar.es/record/111659/files/texto_completo.pdf$$yVersión publicada
000111659 8564_ $$s2448905$$uhttps://zaguan.unizar.es/record/111659/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000111659 909CO $$ooai:zaguan.unizar.es:111659$$particulos$$pdriver
000111659 951__ $$a2024-03-18-12:54:58
000111659 980__ $$aARTICLE