IRCCS Ospedale Pediatrico Bambino Gesù, Dipartimento di Oncoematologia e Terapia Cellulare e Genica, Roma, Italy; Università degli Studi di Pavia, Dipartimento di Scienze Pediatriche, Pavia, Italy.
IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Trends Immunol. 2018 Jul;39(7):577-590. doi: 10.1016/j.it.2018.04.009. Epub 2018 May 21.
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.
自然杀伤 (NK) 细胞参与针对病毒和肿瘤的先天防御。它们的功能通过激活和抑制受体精细调节。在后者中，杀伤免疫球蛋白样受体和 CD94/NKG2A 识别人类白细胞抗原 (HLA) Ⅰ类分子，使 NK 细胞能够区分正常和异常细胞，以及识别同种异体细胞，因为它们能够感知 HLA 多态性。后一种现象在 HLA 单倍体相合造血干细胞移植 (haplo-HSCT) 中起着关键作用，对于高危急性白血病患者来说，他们可以从 NK 同种反应性供体中进行移植。已经开发了不同的 haplo-HSCT 方案，包括 T 细胞耗竭或 T 细胞丰富 - 后者需要移植物抗宿主病预防。一种新的移植物处理方法，基于耗尽 αβ T 细胞和 B 细胞，允许输注完全成熟的 NK 细胞，包括同种反应性 NK 细胞。患者良好的临床结果突显了这些先天细胞在癌症治疗中的重要性。
