Phenotypic and functional characterization of nk cells in αβt-cell and b-cell depleted haplo-hsct to cure pediatric patients with acute leukemia

Raffaella Meazza, Michela Falco, Fabrizio Loiacono, Paolo Canevali, Mariella Della Chiesa, Alice Bertaina, Daria Pagliara, Pietro Merli, Valentina Indio, Federica Galaverna, Mattia Algeri, Francesca Moretta, Natalia Colomar-Carando, Letizia Muccio, Simona Sivori, Andrea Pession, Maria Cristina Mingari, Lorenzo Moretta, Alessandro Moretta, Franco LocatelliDaniela Pende

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number2187
Pages (from-to)1-21
Number of pages21
JournalCancers
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 2020

Keywords

  • Haploidentical hematopoietic stem cell transplantation (HSCT)
  • Human cytomegalovirus (HCMV)
  • Killer Ig-like receptors (KIR)
  • NK alloreactivity
  • NK cells
  • Pediatric acute leukemia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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