Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia
Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia
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DOI：
10.1182/blood.v99.10.3661
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发表时间：
2002-05-15
期刊：
影响因子：
20.3
通讯作者：
Moretta, A
中科院分区：
文献类型：
--
作者：
Costello, RT;Sivori, S;Moretta, A
自然杀伤（NK）细胞的细胞溶解功能由一系列活化受体和辅助受体的参与诱导，其中一些最近已被鉴定并统称为天然细胞毒性受体（NCR）。在这里，我们分析了从急性髓性白血病（AML）患者中获得的NK细胞的细胞溶解功能。与健康供体形成鲜明对比的是，在大多数（18例中的16例）AML患者中，大多数NK细胞显示出低NCR表面密度（NCR dull）。这种表型与对自体白血病细胞的弱细胞溶解活性相关，不能通过单克隆抗体介导的HLA I类/杀伤免疫球蛋白样受体相互作用的破坏来逆转。其余2例患者的特征为NK细胞具有NCRbright表型。令人惊讶的是，尽管显示出NCR介导的细胞溶解活性，但这些NCRbright NK细胞不能杀死自体白血病原始细胞。重要的是，来自这2名患者的白血病原始细胞也对由正常NCRbright同种异体NK细胞介导的溶解具有抗性。我们的研究表明，在大多数情况下，NK细胞不能杀死自体白血病母细胞是由于低NCR表面表达。然而，在少数情况下，这种失败似乎涉及基于与NCR介导的靶细胞识别相关的配体下调的肿瘤逃逸机制。(C)2002年，美国血液学会。
The cytolytic function of natural killer (NK) cells is induced by the engagement of a series of activating receptors and coreceptors some of which have recently been identified and collectively termed natural cytotoxicity receptors (NCRs). Here, we analyzed the cytolytic function of NK cells obtained from patients with acute myelold leukemia (AML). In sharp contrast with healthy donors, in most (16 of 18) patients with AML the majority of NK cells displayed low NCR surface density (NCRdull). This phenotype correlated with a weak cytolytic activity against autologous leukemic cells that could not be reversed by the monoclonal antibody-mediated disruption of HLA class I/killer immunoglobulin like receptor interaction. The remaining 2 patients were characterized by NK cells having an NCRbright phenotype. Surprisingly, although displaying NCR-mediated cytolytic activity, these NCRbright NK cells were unable to kill autologous leukemic blasts, Importantly, the leukemic blasts from these 2 patients were also resistant to lysis mediated by normal NCRbright allogenelc NK cells. Our study suggests that in most instances the inability of NK cells to kill autologous leukemic blasts is consequent to low NCR surface expression. In few cases, however, this failure appears to involve a mechanism of tumor escape based on down-regulation of ligands relevant for NCR-mediated target cell recognition. (C) 2002 by The American Society of Hematology.