Grzywacz Bartosz, Miller Jeffrey S, Verneris Michael R
Division of Blood and Marrow Transplantation, University of Minnesota, MN, USA.
Best Pract Res Clin Haematol. 2008 Sep;21(3):467-83. doi: 10.1016/j.beha.2008.07.008.
Natural killer (NK) cells potentially play a significant role in eradicating residual disease following allogeneic haematopoietic cell transplantation, and have been explored as tools for adoptive immunotherapy for chemotherapy-refractory patients. NK cell cytotoxicity is modulated by multiple activating and inhibitory receptors that maintain a balance between self-tolerance and providing surveillance against pathogens and malignant transformation. The functional characteristics of NK cells are dictated by the strength of inhibitory receptor signalling. Major histocompatibility complex (MHC)-specific inhibitory receptor acquisition occurs sequentially during NK cell development, and is determined by the nature of immunological reconstitution after allogeneic haematopoietic cell transplantation. Polymorphisms of inhibitory receptors [killer immunoglobulin-like receptors (KIRs)] and their ligands (MHC) contribute to interindividual variability. As a result, the functional NK cell repertoire of individual donors has variable potential for graft-vs-leukaemia reactions. Models predicting NK cell alloreactivity, including KIR ligand mismatch and missing KIR ligand strategies, are discussed as algorithms for optimal NK cell donor selection. Future modifications to improve NK cell adoptive immunotherapy by means of increasing target recognition and reducing inhibitory signalling are being explored.
自然杀伤（NK）细胞在异基因造血细胞移植后清除残留疾病方面可能发挥重要作用，并且已被探索作为化疗难治性患者过继性免疫治疗的工具。NK细胞的细胞毒性由多种激活和抑制性受体调节，这些受体在自身耐受与对病原体和恶性转化的监测之间保持平衡。NK细胞的功能特性由抑制性受体信号传导的强度决定。主要组织相容性复合体（MHC）特异性抑制性受体的获得在NK细胞发育过程中依次发生，并由异基因造血细胞移植后的免疫重建性质决定。抑制性受体[杀伤细胞免疫球蛋白样受体（KIR）]及其配体（MHC）的多态性导致个体间的差异。因此，个体供体的功能性NK细胞库对移植物抗白血病反应具有不同的潜力。预测NK细胞同种异体反应性的模型，包括KIR配体错配和缺失KIR配体策略，作为最佳NK细胞供体选择的算法进行了讨论。目前正在探索通过增强靶标识别和减少抑制性信号传导来改进NK细胞过继性免疫治疗的未来改进方法。
