Wodnar-Filipowicz A, Kalberer Christian P
Department of Research, University Hospital Basel, Basel, Switzerland.
Swiss Med Wkly. 2007 Mar 2;137 Suppl 155:25S-30S. doi: 10.4414/smw.2006.11360.
Although progress has been made in the management of acute leukaemias, most patients who fail to respond to front-line therapies with cytostatic agents and stem cell transplantation, or who relapse after an initial response die from progressive disease. Novel treatment modalities exploiting donor-derived natural killer (NK) cells generate an alloreactive graft-versus-leukaemia response and eliminate the residual malignant clones in transplanted patients. NK cells are components of the innate immunity playing an important role in the surveillance of human tumours. Recognition of malignant cells depends on a dynamic balance between antagonistic functions of an array of NK activating and inhibitory receptors. The natural cytotoxicity receptors (NCRs) are NK cell-specific and together with the NKG2D receptor are responsible for NK cell activation and tumour cell killing. The killer immunoglobulin-like receptors (KIRs) recruit phosphatases and can antagonise the activating signals and prevent the cytolytic NK cell programme. Understanding of the integration of these multiple signals at the molecular level is central for exploring the cytolytic function of NK cells. This review describes molecular mechanisms of NK receptor-ligand interactions controlling target cell recognition and addresses the potential of NK cells for the specific elimination of leukaemic clones with the goal of advancing immunotherapy of leukaemia.
尽管在急性白血病的治疗方面已取得进展，但大多数对细胞毒性药物和干细胞移植一线治疗无反应或初始缓解后复发的患者最终死于疾病进展。利用供体来源的自然杀伤（NK）细胞的新型治疗方式可产生同种异体移植物抗白血病反应，并清除移植患者体内残留的恶性克隆。NK细胞是固有免疫的组成部分，在人类肿瘤监测中发挥重要作用。对恶性细胞的识别取决于一系列NK激活受体和抑制受体的拮抗功能之间的动态平衡。自然细胞毒性受体（NCR）是NK细胞特异性的，与NKG2D受体共同负责NK细胞的激活和肿瘤细胞杀伤。杀伤性免疫球蛋白样受体（KIR）募集磷酸酶，可拮抗激活信号并阻止NK细胞的溶细胞程序。在分子水平上理解这些多种信号的整合对于探索NK细胞的溶细胞功能至关重要。本综述描述了控制靶细胞识别的NK受体 - 配体相互作用的分子机制，并探讨了NK细胞特异性清除白血病克隆的潜力，以期推动白血病的免疫治疗。
