000097136 001__ 97136
000097136 005__ 20210902121904.0
000097136 0247_ $$2doi$$a10.1038/s41598-020-76051-z
000097136 0248_ $$2sideral$$a121112
000097136 037__ $$aART-2020-121112
000097136 041__ $$aeng
000097136 100__ $$aCalvo, T.
000097136 245__ $$aExpanded and activated allogeneic NK cells are cytotoxic against B-chronic lymphocytic leukemia (B-CLL) cells with sporadic cases of resistance
000097136 260__ $$c2020
000097136 5060_ $$aAccess copy available to the general public$$fUnrestricted
000097136 5203_ $$aAdoptive transfer of allogeneic natural killer (NK) cells is becoming a credible immunotherapy for hematological malignancies. In the present work, using an optimized expansion/activation protocol of human NK cells, we generate expanded NK cells (eNK) with increased expression of CD56 and NKp44, while maintaining that of CD16. These eNK cells exerted significant cytotoxicity against cells from 34 B-CLL patients, with only 1 sample exhibiting resistance. This sporadic resistance did not correlate with match between KIR ligands expressed by the eNK cells and the leukemic cells, while cells with match resulted sensitive to eNK cells. This suggests that KIR mismatch is not relevant when expanded NK cells are used as effectors. In addition, we found two examples of de novo resistance to eNK cell cytotoxicity during the clinical course of the disease. Resistance correlated with KIR-ligand match in one of the patients, but not in the other, and was associated with a significant increase in PD-L1 expression in the cells from both patients. Treatment of one of these patients with idelalisib correlated with the loss of PD-L1 expression and with re-sensitization to eNK cytotoxicity. We confirmed the idelalisib-induced decrease in PD-L1 expression in the B-CLL cell line Mec1 and in cultured cells from B-CLL patients. As a main conclusion, our results reinforce the feasibility of using expanded and activated allogeneic NK cells in the treatment of B-CLL.
000097136 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2016-76338-R$$9info:eu-repo/grantAgreement/ES/DGA/B31-17R
000097136 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000097136 590__ $$a4.379$$b2020
000097136 591__ $$aMULTIDISCIPLINARY SCIENCES$$b17 / 73 = 0.233$$c2020$$dQ1$$eT1
000097136 592__ $$a1.24$$b2020
000097136 593__ $$aMultidisciplinary$$c2020$$dQ1
000097136 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000097136 700__ $$aReina-Ortiz, C.
000097136 700__ $$aGiraldos, D.
000097136 700__ $$0(orcid)0000-0002-3854-2687$$aGascón, M.$$uUniversidad de Zaragoza
000097136 700__ $$aWoods, D.
000097136 700__ $$aAsenjo, J.
000097136 700__ $$aMarco-Brualla, J.
000097136 700__ $$0(orcid)0000-0001-5068-7355$$aAzaceta, G.$$uUniversidad de Zaragoza
000097136 700__ $$aIzquierdo, I.$$uUniversidad de Zaragoza
000097136 700__ $$0(orcid)0000-0001-8515-3599$$aPalomera, L.$$uUniversidad de Zaragoza
000097136 700__ $$aSánchez-Martínez, D.
000097136 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, I.$$uUniversidad de Zaragoza
000097136 700__ $$0(orcid)0000-0003-2156-8378$$aNaval, J.$$uUniversidad de Zaragoza
000097136 700__ $$aVilches, C.
000097136 700__ $$aVillalba, M.
000097136 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, A.$$uUniversidad de Zaragoza
000097136 7102_ $$11003$$2027$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Anatom.Embriol.Humana
000097136 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000097136 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000097136 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000097136 773__ $$g10, 1 (2020), 19398 [14 pp]$$pSci. rep.$$tScientific Reports$$x2045-2322
000097136 8564_ $$s859705$$uhttps://zaguan.unizar.es/record/97136/files/texto_completo.pdf$$yVersión publicada
000097136 8564_ $$s290614$$uhttps://zaguan.unizar.es/record/97136/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000097136 909CO $$ooai:zaguan.unizar.es:97136$$particulos$$pdriver
000097136 951__ $$a2021-09-02-10:38:25
000097136 980__ $$aARTICLE