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Open AccessArticle

Phenotypic and Functional Characterization of NK Cells in αβT-Cell and B-Cell Depleted Haplo-HSCT to Cure Pediatric Patients with Acute Leukemia

1
Laboratory of Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16132 Genoa, Italy
2
Laboratory of Clinical and Experimental Immunology, Integrated Department of Services and Laboratories, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy
3
Department of Experimental Medicine, Centre of Excellence for Biomedical Research, University of Genoa, 16132 Genoa, Italy
4
Department of Hematology/Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy
5
Giorgio Prodi Interdepartmental Center for Cancer Research—CIRC, University of Bologna, 40138 Bologna, Italy
6
Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy
7
Department of Pediatrics, University of Bologna, 40138 Bologna, Italy
8
Department of Immunology, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy
9
Department of Gynecology/Obstetrics and Pediatrics, Sapienza University, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
A.B. present address: Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA 94305, USA.
F.M. present address: Department of Laboratory Medicine, IRCCS Sacro Cuore Don Calabria Hospital, 37024 Negrar, Italy.
§
These authors contributed equally to this work.
Cancers 2020, 12(8), 2187; https://doi.org/10.3390/cancers12082187
Received: 26 June 2020 / Revised: 31 July 2020 / Accepted: 1 August 2020 / Published: 5 August 2020
(This article belongs to the Special Issue NK/ILCs in Tumors)
NK cells can exert remarkable graft-versus-leukemia (GvL) effect in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Here, we dissected the NK-cell repertoire of 80 pediatric acute leukemia patients previously reported to have an excellent clinical outcome after αβT/B-depleted haplo-HSCT. This graft manipulation strategy allows the co-infusion of mature immune cells, mainly NK and γδT cells, and hematopoietic stem cells (HSCs). To promote NK-cell based antileukemia activity, 36/80 patients were transplanted with an NK alloreactive donor, defined according to the KIR/KIR-Ligand mismatch in the graft-versus-host direction. The analysis of the reconstituted NK-cell repertoire in these patients showed relatively high proportions of mature and functional KIR+NKG2ACD57+ NK cells, including the alloreactive NK cell subset, one month after HSCT. Thus, the NK cells adoptively transfused with the graft persist as a mature source of effector cells while new NK cells differentiate from the donor HSCs. Notably, the alloreactive NK cell subset was endowed with the highest anti-leukemia activity and its size in the reconstituted repertoire could be influenced by human cytomegalovirus (HCMV) reactivation. While the phenotypic pattern of donor NK cells did not impact on post-transplant HCMV reactivation, in the recipients, HCMV infection/reactivation fostered a more differentiated NK-cell phenotype. In this cohort, no significant correlation between differentiated NK cells and relapse-free survival was observed. View Full-Text
Keywords: NK cells; haploidentical hematopoietic stem cell transplantation (HSCT); killer Ig-like receptors (KIR); NK alloreactivity; pediatric acute leukemia; human cytomegalovirus (HCMV) NK cells; haploidentical hematopoietic stem cell transplantation (HSCT); killer Ig-like receptors (KIR); NK alloreactivity; pediatric acute leukemia; human cytomegalovirus (HCMV)
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MDPI and ACS Style

Meazza, R.; Falco, M.; Loiacono, F.; Canevali, P.; Della Chiesa, M.; Bertaina, A.; Pagliara, D.; Merli, P.; Indio, V.; Galaverna, F.; Algeri, M.; Moretta, F.; Colomar-Carando, N.; Muccio, L.; Sivori, S.; Pession, A.; Mingari, M.C.; Moretta, L.; Moretta, A.; Locatelli, F.; Pende, D. Phenotypic and Functional Characterization of NK Cells in αβT-Cell and B-Cell Depleted Haplo-HSCT to Cure Pediatric Patients with Acute Leukemia. Cancers 2020, 12, 2187. https://doi.org/10.3390/cancers12082187

AMA Style

Meazza R, Falco M, Loiacono F, Canevali P, Della Chiesa M, Bertaina A, Pagliara D, Merli P, Indio V, Galaverna F, Algeri M, Moretta F, Colomar-Carando N, Muccio L, Sivori S, Pession A, Mingari MC, Moretta L, Moretta A, Locatelli F, Pende D. Phenotypic and Functional Characterization of NK Cells in αβT-Cell and B-Cell Depleted Haplo-HSCT to Cure Pediatric Patients with Acute Leukemia. Cancers. 2020; 12(8):2187. https://doi.org/10.3390/cancers12082187

Chicago/Turabian Style

Meazza, Raffaella; Falco, Michela; Loiacono, Fabrizio; Canevali, Paolo; Della Chiesa, Mariella; Bertaina, Alice; Pagliara, Daria; Merli, Pietro; Indio, Valentina; Galaverna, Federica; Algeri, Mattia; Moretta, Francesca; Colomar-Carando, Natalia; Muccio, Letizia; Sivori, Simona; Pession, Andrea; Mingari, Maria C.; Moretta, Lorenzo; Moretta, Alessandro; Locatelli, Franco; Pende, Daniela. 2020. "Phenotypic and Functional Characterization of NK Cells in αβT-Cell and B-Cell Depleted Haplo-HSCT to Cure Pediatric Patients with Acute Leukemia" Cancers 12, no. 8: 2187. https://doi.org/10.3390/cancers12082187

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