| Home > Articles > The metabolism of cells regulates their sensitivity to NK cells depending on p53 status > MARC |
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
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