KIR基因与异基因造血细胞移植

异基因造血细胞移植后，供体细胞所拥有的强大而持久的免疫治疗功效已越来越为人所熟知。本文对2001—2003年具有代表性的关于识别肿瘤靶细胞的KIR和其他NK细胞受体，以及在亲缘移植和无血缘移植时供受者对的KIR多态性的最新文献予以综述。异源反应性NK细胞活性是T细胞异源反应活性以外的，具有显著的抗肿瘤／白血病活性(GVL)的自然免疫现象。KIR基因以及配体的研究结果揭示了NK细胞自我识别和攻击靶细胞对于异基因造血细胞移植(Allo-HCT)预后的有利影响。NK细胞通过特异性杀伤宿主抗原呈递细胞(APC)，促进残存宿主细胞的清除以及识别和攻击宿主白血病细胞(GVL作用)以达到降低GVHD发生率和移植后白血病复发率之目的。开展NK细胞异源反应活性细胞的诱导、鉴定及分选技术，研发及采用可应用于临床治疗的NK细胞抑制型受体阻滞剂，上调或加强异源反应性NK细胞活性均有可能显著提高移植物抗白血病(GVL)效应。进一步研究KIR抑制型受体的调控将有助于今后癌症免疫治疗新战略及对策的制定。

KIR and Allogeneic Hematopoietic Cell Transplantation -- Review

The profound graft-versus-leukemia (GVL) effect presented after allogeneic hematopoietic cell transplantation (allo-HSCT) has been evidenced. In contrast to T cell mediated GVL, natural killer (NK) cells recognize target cells and introduce GVL effect by using an integration of activating and inhibitory receptors. This review has summarized current literatures from 2001-2003 on human killer cell immunoglobulin receptors (KIR) and other NK cell receptors involved in recognition of tumor targets and the polymorphism of KIR genes of donor/recipient pairs of related and unrelated Allo-HSCT. KIR epitope mismatch may facilitate engraftment and reduce leukemia relapse post transplant by mediating lysis of recipient's cells and introducing GVL effect under the condition of KIR epitope mismatch. Clinical roles of KIR in Allo-HSCT and immunotherapy are discussed. Technologic approach in allogeneic reactive NK cells introduction, identification and selection in vitro , development of inhibitory receptor blockade as well as up-regulation of activating NK cells may significantly enhance GVL immune response. Further investigation on the regulation of KIR inhibitory receptors enables to design novel strategy in cancer immunotherapy over the forthcoming decade.