TY - JOUR
T1 - NK Cells Mediate a Crucial Graft-versus-Leukemia Effect in Haploidentical-HSCT to Cure High-Risk Acute Leukemia
AU - Locatelli, Franco
AU - Pende, Daniela
AU - Falco, Michela
AU - Della Chiesa, Mariella
AU - Moretta, Alessandro
AU - Moretta, Lorenzo
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
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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U2 - 10.1016/j.it.2018.04.009
DO - 10.1016/j.it.2018.04.009
M3 - Review article
AN - SCOPUS:85047188414
VL - 39
SP - 577
EP - 590
JO - Trends in Immunology
JF - Trends in Immunology
SN - 1471-4906
IS - 7
ER -