title: Natural killer cells in the treatment of high-risk acute leukaemia.
abstract: Several studies have shown that in patients with acute leukaemia given allogeneic haematopoietic stem cell transplantation (allo-HSCT) large part of the therapeutic effect lies on the anti-tumour effect displayed by cells of both adaptive and innate immunity. This evidence has also opened new scenarios for the treatment of patients with other haematological malignancies/solid tumours. In particular, donor-derived natural killer (NK) cells play a crucial role in the eradication of cancer cells in patients given an allograft from an HLA-haploidentical relative, especially when there is a killer inhibitory-receptor (KIR)-KIR ligand mismatched in the donor-recipient direction. Alloreactive donor-derived NK cells have been also demonstrated to kill recipient antigen-presenting cells and cytotoxic T lymphocytes, thus preventing graft-versus-host disease (GvHD) and graft rejection and to largely contribute to the defence against cytomegalovirus infection in the early post-transplant period. Several clinical studies have recently focused also on the influence of NK-cell activating receptors on the outcome of allo-HSCT recipients; in particular, B/x haplotype donors offer clinical advantages compared with A/A donors, even when the donor is an HLA-identical volunteer. Altogether, these data have provided the rationale for implementing phase I/II clinical trials based on adoptive infusion of either selected or ex vivo activated NK cells from an HLA-mismatched donor. This review summarizes the biological and clinical data on the role played by NK cells in patients with high-risk acute leukaemia, focusing also on the still unsolved issues and the future perspectives related to the approaches of adoptive NK cell therapy.
authors.affiliation: Department of Paediatric Haematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy; University of Pavia, Pavia, Italy. Electronic address: franco.locatelli@opbg.net.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Department of Paediatric Haematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Moretta
authors.affiliation: Department of Paediatric Haematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Brescia
authors.affiliation: Department of Paediatric Haematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Merli
mesh_terms: D000208:Acute Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D007938:Leukemia / Q000276:immunology* / Q000628:therapy*; D014019:Tissue Donors; D014184:Transplantation, Homologous
keywords: Adoptive immunotherapy with NK cells; Allogeneic hematopoietic stem cell transplantation; Inhibitory and activating NK-cell receptors; Innate immunity; KIR–KIR ligand mismatched; Redirection of NK-cell cytotoxicity