000058477 001__ 58477
000058477 005__ 20200221144318.0
000058477 0247_ $$2doi$$a10.3389/fimmu.2016.00454
000058477 0248_ $$2sideral$$a97584
000058477 037__ $$aART-2016-97584
000058477 041__ $$aeng
000058477 100__ $$aSánchez-Martínez, D.
000058477 245__ $$aActivated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells
000058477 260__ $$c2016
000058477 5060_ $$aAccess copy available to the general public$$fUnrestricted
000058477 5203_ $$aMutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs) the most effective stimulus to activate NK cells. Here, we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell-activating receptors (NKG2D and NCRs) and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV) are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells, and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.
000058477 536__ $$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/SAF2011-25390$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1-R
000058477 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000058477 590__ $$a6.429$$b2016
000058477 591__ $$aIMMUNOLOGY$$b21 / 150 = 0.14$$c2016$$dQ1$$eT1
000058477 592__ $$a3.033$$b2016
000058477 593__ $$aImmunology and Allergy$$c2016$$dQ1
000058477 593__ $$aImmunology$$c2016$$dQ1
000058477 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000058477 700__ $$aLanuza, P.M.
000058477 700__ $$aGómez, N.
000058477 700__ $$aMuntasell, A.
000058477 700__ $$aCisneros, E.
000058477 700__ $$aMoraru, M.
000058477 700__ $$0(orcid)0000-0001-5068-7355$$aAzaceta, G.
000058477 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, A.$$uUniversidad de Zaragoza
000058477 700__ $$0(orcid)0000-0003-3043-147X$$aMartínez-Lostao, L.$$uUniversidad de Zaragoza
000058477 700__ $$aVillalba, M.
000058477 700__ $$0(orcid)0000-0001-8515-3599$$aPalomera, L.$$uUniversidad de Zaragoza
000058477 700__ $$aVilches, C.
000058477 700__ $$aGarcía Marco, J.A.
000058477 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000058477 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000058477 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000058477 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000058477 773__ $$g7 (2016), 454 [11 pp]$$pFront. immunol.$$tFrontiers in Immunology$$x1664-3224
000058477 8564_ $$s264210$$uhttps://zaguan.unizar.es/record/58477/files/texto_completo.pdf$$yVersión publicada
000058477 8564_ $$s100073$$uhttps://zaguan.unizar.es/record/58477/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000058477 909CO $$ooai:zaguan.unizar.es:58477$$particulos$$pdriver
000058477 951__ $$a2020-02-21-13:40:24
000058477 980__ $$aARTICLE