000112423 001__ 112423
000112423 005__ 20240319080951.0
000112423 0247_ $$2doi$$a10.1038/s41598-022-07281-6
000112423 0248_ $$2sideral$$a128373
000112423 037__ $$aART-2022-128373
000112423 041__ $$aeng
000112423 100__ $$aBelkahla, Sana
000112423 245__ $$aThe metabolism of cells regulates their sensitivity to NK cells depending on p53 status
000112423 260__ $$c2022
000112423 5060_ $$aAccess copy available to the general public$$fUnrestricted
000112423 5203_ $$aLeukemic cells proliferate faster than non-transformed counterparts. This requires them to change their metabolism to adapt to their high growth. This change can stress cells and facilitate recognition by immune cells such as cytotoxic lymphocytes, which express the activating receptor Natural Killer G2-D (NKG2D). The tumor suppressor gene p53 regulates cell metabolism, but its role in the expression of metabolism-induced ligands, and subsequent recognition by cytotoxic lymphocytes, is unknown. We show here that dichloroacetate (DCA), which induces oxidative phosphorylation (OXPHOS) in tumor cells, induces the expression of such ligands, e.g. MICA/B, ULBP1 and ICAM-I, by a wtp53-dependent mechanism. Mutant or null p53 have the opposite effect. Conversely, DCA sensitizes only wtp53-expressing cells to cytotoxic lymphocytes, i.e. cytotoxic T lymphocytes and NK cells. In xenograft in vivo models, DCA slows down the growth of tumors with low proliferation. Treatment with DCA, monoclonal antibodies and NK cells also decreased tumors with high proliferation. Treatment of patients with DCA, or a biosimilar drug, could be a clinical option to increase the effectiveness of CAR T cell or allogeneic NK cell therapies.
000112423 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B31-20R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00
000112423 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000112423 590__ $$a4.6$$b2022
000112423 592__ $$a0.973$$b2022
000112423 591__ $$aMULTIDISCIPLINARY SCIENCES$$b22 / 73 = 0.301$$c2022$$dQ2$$eT1
000112423 593__ $$aMultidisciplinary$$c2022$$dQ1
000112423 594__ $$a7.5$$b2022
000112423 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000112423 700__ $$aBrualla, Joaquín Marco$$uUniversidad de Zaragoza
000112423 700__ $$aFayd'herbe de Maudave, Alexis
000112423 700__ $$aFalvo, Paolo
000112423 700__ $$aAllende-Vega, Nerea
000112423 700__ $$aConstantinides, Michael
000112423 700__ $$aKhan, Abrar Ul Haq
000112423 700__ $$aCoenon, Lois
000112423 700__ $$aAlexia, Catherine
000112423 700__ $$aMitola, Giulia
000112423 700__ $$aMassa, Paul
000112423 700__ $$aOrecchioni, Stefania
000112423 700__ $$aBertolini, Francesco
000112423 700__ $$aMnif, Wissem
000112423 700__ $$aHernandez, Javier
000112423 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, Alberto$$uUniversidad de Zaragoza
000112423 700__ $$aVillalba, Martin
000112423 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000112423 773__ $$g12 (2022), 3234 [13 pp.]$$pSci. rep. (Nat. Publ. Group)$$tScientific reports (Nature Publishing Group)$$x2045-2322
000112423 8564_ $$s1309923$$uhttps://zaguan.unizar.es/record/112423/files/texto_completo.pdf$$yVersión publicada
000112423 8564_ $$s2693335$$uhttps://zaguan.unizar.es/record/112423/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000112423 909CO $$ooai:zaguan.unizar.es:112423$$particulos$$pdriver
000112423 951__ $$a2024-03-18-13:02:52
000112423 980__ $$aARTICLE