期刊
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
卷 164, 期 4, 页码 253-264出版社
KARGER
DOI: 10.1159/000365632
关键词
Natural killer cells; Killer Ig-like receptors; Activating NK receptors; NK-tumor cell interactions; Haploidentical hematopoietic stem cell transplantation
资金
- Associazione Italiana Ricerca sul Cancro (AIRC): IG project [10225]
- Special Program Molecular Clinical Oncology 5 x 1000' project [9962]
- Ministero della Salute: RF Project [RF-2010-2316606]
- MIUR-PRIN project [2009T4TC33_004]
- Ricerca Finalizzata [RF-IG-2008-1200689]
- Progetto Ricerca Ateneo
- International Leibniz Research Cluster (ILRC) Network project 'ImmunoMemory' - Senatsausschuss Wettbewerb (SAW)
- Fondazione Italiana per la Ricerca sul Cancro (FIRC)
Natural killer (NK) cells are important effectors playing a relevant role in innate immunity, primarily in tumor surveillance and in defenses against viruses. Human NK cells recognize HLA class I molecules through surface receptors (KIR and NKG2A) that inhibit NK cell function and kill target cells that have lost (or underexpress) HLA class I molecules as it occurs in tumors or virus-infected cells. NK cell activation is mediated by an array of activating receptors and co-receptors that recognize ligands expressed primarily on tumors or virus-infected cells. In vivo anti-tumor NK cell activity may be suppressed by tumor or tumor-associated cells. Alloreactive NK cells (i.e. those that are not inhibited by the HLA class I alleles of the patient) derived from HSC of haploidentical donors play a major role in the cure of high-risk leukemia, by killing leukemia blasts and patient's DC, thus preventing tumor relapses and graft-versus-host disease. The expression of the HLA-C2-specific activating KIR2DS1 may also contribute to NK alloreactivity in patients expressing C2 alleles. A clear correlation has been proven between the size of the alloreactive NK cell population and the clinical outcome. Recently, haplo-HSCT has been further improved with the direct infusion, together with HSC, of donor-derived, mature alloreactive NK cells and TCR gamma delta(+) T cells - both contributing to a prompt anti-leukemia effect together with an efficient defense against pathogens during the 6- to 8-week interval required for the generation of alloreactive NK cells from HSC. (C) 2014 S. Karger AG, Basel
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