Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Curr Opin Hematol. 2012 Nov;19(6):421-6. doi: 10.1097/MOH.0b013e3283590395.
This article reviews the impact of natural killer (NK) cell alloreactivity on hematopoietic cell transplantation since it was first observed in haploidentical transplant recipients 10 years ago.
Research has established 'missing self-recognition' as the mechanism underlying NK cell-mediated graft-versus-leukemia effects in T-cell-depleted haploidentical hematopoietic cell transplantation and has clarified optimal transplantation protocols to harness NK cell alloreactivity.
In the past decade, clinical studies have shown that the benefits of donor-versus-recipient NK cell alloreactivity in haploidentical transplantation are triggered by specific human leukocyte antigen (HLA) class I mismatches. Donor HLA is crucial for driving NK cell education so that reconstituting NK cells mature as donor-tolerant and recipient-alloreactive. Transplantation of large doses of extensively T-cell-depleted hematopoietic grafts with no posttransplant immune suppression was found to be essential for development of NK cell alloreactivity. Clinical trials demonstrated that donor-versus-recipient NK cell alloreactivity is a key therapeutic element in haploidentical transplants for acute myeloblastic leukemia in adults and acute lymphoblastic leukemia in children. Moreover, in pilot studies, mature haploidentical NK cells were transiently transferred into lymphoablated patients with acute leukemia in remission. The results showed NK cell therapy may be a promising strategy for consolidating leukemia remission. In line with the notion that NK cell function is regulated by a balance between activating and inhibitory receptors, in the matched transplant setting, transplantation from donors possessing certain activating NK receptors (activating killer cell immunoglobulin-like receptors) appeared to protect from relapse and improved survival.
本文回顾了自然杀伤 (NK) 细胞同种异体反应性对造血细胞移植的影响，该影响是 10 年前在单倍体相合移植受者中首次观察到的。
研究已经确定“自身缺失识别”是 T 细胞耗竭的单倍体相合造血细胞移植中 NK 细胞介导移植物抗白血病效应的机制，并阐明了利用 NK 细胞同种异体反应性的最佳移植方案。
在过去的十年中，临床研究表明，在单倍体相合移植中，供体与受者 NK 细胞同种异体反应性的益处是由特定的人类白细胞抗原 (HLA) Ⅰ类错配触发的。供体 HLA 对于驱动 NK 细胞的教育至关重要，以使重建的 NK 细胞成熟为供体耐受和受者同种异体反应性。研究发现，移植大量经过充分 T 细胞耗竭的造血移植物而不进行移植后免疫抑制是 NK 细胞同种异体反应性发展的必要条件。临床试验表明，供体与受者 NK 细胞同种异体反应性是成人急性髓细胞白血病和儿童急性淋巴细胞白血病单倍体相合移植中的关键治疗因素。此外，在试点研究中，成熟的单倍体 NK 细胞被短暂转移到处于缓解期的急性白血病淋巴耗竭患者中。结果表明 NK 细胞治疗可能是巩固白血病缓解的一种有前途的策略。与 NK 细胞功能受激活和抑制受体之间平衡调节的观点一致，在匹配的移植环境中，来自具有某些激活 NK 受体（激活杀伤细胞免疫球蛋白样受体）的供体的移植似乎可以防止复发并提高生存率。
