期刊
FRONTIERS IN IMMUNOLOGY
卷 4, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2013.00015
关键词
natural killer cells; killer Ig-like receptors; NK alloreactivity; acute myeloid leukemia; acute lymphoblastic leukemia; haploidentical hemopoietic stem cell transplantation; graft-vs-host disease
类别
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC): IG project [4725]
- Special Program Molecular Clinical Oncology [9962]
- MIUR-PRIN project [20077NFBH8_005, 2008PTB3HC_005]
- Ministero della Salute: RF-Ricerca Oncologica-Project of Integrated Program [RO-strategici 3/07, RFPS-2007-4-633146, RO-strategici 8/07]
Natural killer (NK) cells are involved in innate immune responses and play a major role in tumor surveillance and in defense against viruses. Human NK cells recognize human leukocyte antigen (HLA) class I molecules via surface receptors [killer immunoglobulin-like receptor (KIR) and NKG2A1 delivering signals that inhibit NK cell function and kill HLA class I-deficient target cells, a frequent event in tumors or virus-infected cells. NK cell triggering is mediated by activating receptors that recognize ligands expressed primarily on tumors or virus-infected cells. NK cells play also a key role in the cure of high-risk leukemias. Thus, donor-derived alloreactive NK cells are fundamental effectors in adult acute myeloid leukemia and in pediatric acute lymphoblastic leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT). Alloreactive NK cells mediate killing of leukemia cells and patient's dendritic cell, thus preventing respectively leukemic relapses and graft-vs-host responses. Cytofluorimetric analysis of KIRs expressed by NK cells allows to define the size of the alloreactive NK subset and the selection of the best potential donor. Recently, it has been shown that also the expression of activating KIRs, in particular the (C2-specific) KIR2DS1, may contribute to donor NK alloreactivity. It has also been established a correlation between the size of the alloreactive NK cell population and the clinical outcome. Notably, the alloreactive NK cells derived from donor's hematopoietic stem cells are generated and persist in patients overtime. The high survival rates of patients undergoing haploidentical HSCT highlight an important new reality in the setting of allograft performed to cure otherwise fatal leukemias. Novel approaches are in progress to further improve the clinical outcome based on the infusion of donor alloreactive NK cells either as a component of the transplanted cell population or as in vitro expanded NK cells.
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