Natural killer alloeffector responses in haploidentical hemopoietic stem cell transplantation to treat high-risk leukemias.
Natural killer (NK) cells, a major cell type of the innate immunity, express surface receptors that regulate potent effector functions such as cytolytic activity and release of cytokines playing a central role in inflammatory response and immunoregulation. In this contribution, we briefly outline the major steps from the discovery of human leukocyte antigen (HLA)-class I-specific inhibitory receptors in humans to recent successful clinical applications in the cure of high-risk leukemias both in adults and in pediatric patients. A central role is played by 'alloreactive' NK cells originated from donor's CD 34(+) cells in eradicating leukemic cells in the setting of T-cell-depleted haploidentical hemopoietic stem cell transplantation. Because alloreactive NK cells play a central role also in preventing graft rejection and graft-vs-host disease, they may represent an ideal tool to treat patients affected by acute high-risk leukemias.
Moretta
L
L
Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy. lorenzomoretta@ospedale-gaslini.ge.it
Locatelli
F
F
Pende
D
D
Mingari
M C
MC
Moretta
A
A
D000208:Acute Disease; D000328:Adult; D002648:Child; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D007938:Leukemia / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D007962:Leukocytes / Q000276:immunology; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology
D015395:Histocompatibility Antigens Class I