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选择异基因造血细胞移植供者以优化自然杀伤细胞的同种异体反应性。

Selection of allogeneic hematopoietic cell transplant donors to optimize natural killer cell alloreactivity.

机构信息

Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell School of Medicine, New York, NY.

Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell School of Medicine, New York, NY; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY.

出版信息

Semin Hematol. 2020 Oct;57(4):167-174. doi: 10.1053/j.seminhematol.2020.10.005. Epub 2020 Nov 7.

Abstract

Natural killer (NK) cells are potent mediators of the graft versus leukemia phenomenon critical to the success of allogeneic hematopoietic cell transplantation. Central to calibrating NK effector function via their interaction with class I human leukocyte antigens are the numerous inhibitory killer Ig-like receptors (KIR). The KIR receptors are encoded by a family of polymorphic genes, whose expression is largely stochastic and uninfluenced by human leukocyte antigens genotype. These features provide the opportunity to select hematopoietic cell donors with favorable KIR genotypes that confer enhanced protection from relapse via NK-mediated graft versus leukemia. Over the last 2 decades, a large body of work has emerged examining the use of KIR genotyping to stratify potential donors based on anticipated NK alloreactivity. Overall, these results support KIR-based donor selection for patients undergoing allogeneic hematopoietic cell transplantation for a diagnosis of acute myelogenous leukemia. Despite this, the underlying factors that control NK cell responsiveness are not completely understood, and opportunities remain to refine donor selection using NK cell receptor genotyping. In this review, we will summarize the relevant findings with respect to KIR genotyping as a selection parameter for allogeneic hematopoietic cell donors and address practical considerations with respect to KIR-based selection of donors for patients with myeloid neoplasia.

摘要

自然杀伤 (NK) 细胞是移植物抗白血病现象的有力介质,对异基因造血细胞移植的成功至关重要。通过与 I 类人白细胞抗原的相互作用来调节 NK 效应功能的核心是众多抑制性杀伤免疫球蛋白样受体 (KIR)。KIR 受体由一组多态性基因编码,其表达在很大程度上是随机的,不受人类白细胞抗原基因型的影响。这些特征为选择具有有利 KIR 基因型的造血细胞供体提供了机会,通过 NK 介导的移植物抗白血病来增强对复发的保护。在过去的 20 年中,大量的研究涌现出来,研究了使用 KIR 基因分型根据预期的 NK 同种异体反应性对潜在供体进行分层。总的来说,这些结果支持基于 KIR 的供体选择,用于接受异基因造血细胞移植以诊断急性髓系白血病的患者。尽管如此,控制 NK 细胞反应性的潜在因素仍不完全清楚,并且仍然有机会使用 NK 细胞受体基因分型来完善供体选择。在这篇综述中,我们将总结与 KIR 基因分型作为异基因造血细胞供体选择参数相关的相关发现,并讨论基于 KIR 的供体选择在髓系肿瘤患者中的实际考虑因素。

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