NK Cells Mediate a Crucial Graft-versus-Leukemia Effect in Haploidentical-HSCT to Cure High-Risk Acute Leukemia

Franco Locatelli, Daniela Pende, Michela Falco, Mariella Della Chiesa, Alessandro Moretta, Lorenzo Moretta

Research output: Contribution to journalReview article

Abstract

Natural killer (NK) cells are involved in innate defenses against viruses and tumors. Their function is finely tuned by activating and inhibitory receptors. Among the latter, killer immunoglobulin-like receptors and CD94/NKG2A recognize human leukocyte antigen (HLA) Class I molecules, allowing NK cells to discriminate between normal and aberrant cells, as well as to recognize allogeneic cells, because of their ability to sense HLA polymorphisms. This latter phenomenon plays a key role in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for high-risk acute leukemia patients transplanted from an NK-alloreactive donor. Different haplo-HSCT settings have been developed, either T depleted or T replete - the latter requiring graft-versus-host disease prophylaxis. A novel graft manipulation, based on depletion of αβ T cells and B cells, allows infusion of fully mature, including alloreactive, NK cells. The excellent patient clinical outcome underscores the importance of these innate cells in cancer therapy.

Original languageEnglish
Pages (from-to)577-590
Number of pages14
JournalTrends in Immunology
Volume39
Issue number7
DOIs
Publication statusPublished - Jul 2018

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HLA Antigens
Natural Killer Cells
Leukemia
Hematopoietic Stem Cell Transplantation
Transplants
KIR Receptors
Oncogenic Viruses
Graft vs Host Disease
B-Lymphocytes
Tissue Donors
T-Lymphocytes
Neoplasms
Therapeutics

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NK Cells Mediate a Crucial Graft-versus-Leukemia Effect in Haploidentical-HSCT to Cure High-Risk Acute Leukemia. / Locatelli, Franco; Pende, Daniela; Falco, Michela; Della Chiesa, Mariella; Moretta, Alessandro; Moretta, Lorenzo.

In: Trends in Immunology, Vol. 39, No. 7, 07.2018, p. 577-590.

Research output: Contribution to journalReview article

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AU - Pende, Daniela

AU - Falco, Michela

AU - Della Chiesa, Mariella

AU - Moretta, Alessandro

AU - Moretta, Lorenzo

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

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AB - Natural killer (NK) cells are involved in innate defenses against viruses and tumors. Their function is finely tuned by activating and inhibitory receptors. Among the latter, killer immunoglobulin-like receptors and CD94/NKG2A recognize human leukocyte antigen (HLA) Class I molecules, allowing NK cells to discriminate between normal and aberrant cells, as well as to recognize allogeneic cells, because of their ability to sense HLA polymorphisms. This latter phenomenon plays a key role in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for high-risk acute leukemia patients transplanted from an NK-alloreactive donor. Different haplo-HSCT settings have been developed, either T depleted or T replete - the latter requiring graft-versus-host disease prophylaxis. A novel graft manipulation, based on depletion of αβ T cells and B cells, allows infusion of fully mature, including alloreactive, NK cells. The excellent patient clinical outcome underscores the importance of these innate cells in cancer therapy.

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