Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma
Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma
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DOI：
10.1200/jco.2003.05.013
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发表时间：
2003-11-01
影响因子：
45.3
通讯作者：
Levy, R
中科院分区：
文献类型：
--
作者：
Weng, WK;Levy, R
目的：虽然利妥昔单抗目前被常规用于治疗B细胞性非霍奇金淋巴瘤，但其抗肿瘤作用的机制尚不清楚。一种潜在的作用机制涉及抗体依赖的细胞毒性(ADCC)。ADCC的两个方面影响这一过程的有效性：肿瘤细胞的敏感性和效应细胞通过其免疫球蛋白G片段C受体(FcGammaRs)激活。已发现几种FcGammaR基因多态性可能影响自然杀伤细胞和巨噬细胞的意愿功能。患者和方法：检测43例滤泡性淋巴瘤患者治疗前的肿瘤细胞对利妥昔单抗介导的ADCC的内在敏感性。此外，对87例患者进行了FcGammaRIIa(CD16)和FcGammaRIIa(CD32)基因多态性检测。结果：临床对利妥昔单抗有反应的患者和无反应的患者的肿瘤易感性没有差异。相反，FcGammaRIIa 158 valine/valine和FcGammaRIIa 131组氨酸/组氨酸基因型均被发现与缓解率和进展自由独立相关。结论：这些数据支持ADCC在效应细胞水平上在利妥昔单抗临床疗效中发挥重要作用的假设。在未来的利妥昔单抗治疗试验中，包括Fc受体基因多态性的信息将是重要的。(C)2003年，由美国临床肿瘤学会提供。
Purpose: Although rituximab is now routinely used in the treatment of B-cell non-Hodgkin's lymphoma, the mechanism of its antitumor effect is not clear. One potential mechanism of action involves antibody-dependent cellular cytotoxicity (ADCC). Two aspects of ADCC influence the effectiveness of this process: the susceptibility of tumor cells and the activation of effector cells via their immunoglobulin G fragment C receptors (FcgammaRs). Several FcgammaR polymorphisms have been identified that may affect the Willing function of natural killer cells and macrophages.Patients and Methods: The pretreatment tumor cells from 43 patients with follicular lymphoma were tested for their intrinsic susceptibility to rituximab-mediated ADCC. in addition, the FcgammaRIIa (CD16) and FcgammaRIIa (CD32) polymorphisms were determined in an expanded group of 87 patients. The results were then correlated with clinical outcome of these patients.Results: No difference was found between the susceptibility of tumors from patients who clinically responded to rituximab versus those who did not respond. Conversely, both the FcgammaRIIa 158 valine/valine and the FcgammaRIIa 131 histidine/histidine genotypes were found to be independently associated with the response rate and freedom from progression.Conclusion: These data support the hypothesis that ADCC plays an important role in the clinical effect of rituximab at the level of the effector cell. it will be important to include information on Fc receptor polymorphisms in future trials of rituximab therapy. (C) 2003 by American Society of Clinical Oncology.