白细胞介素2增强利妥昔单抗介导的细胞毒杀伤效应机制研究  

Interlenkino2 improves the antitumor activity of Rituximab in patients with B-cell lymphoma in vitro

作　　者：张文霞[1] 郭军[1] 林保和[1] 孟松娘[1] 王小沛[1] 谢彦[1] 郑文[1] 张运涛[1] 朱军[1] 

机构地区：[1]北京大学临床肿瘤学院、北京肿瘤医院,100036

出　　处：《中华血液学杂志》2007年第1期41-44,共4页Chinese Journal of Hematology

基　　金：国家自然科学基金资助项目（30571758）

摘　　要：目的建立预测利妥昔单抗治疗B细胞淋巴瘤疗效的体外方法，探讨白细胞介素2（IL-2）增强利妥昔单抗介导的细胞毒杀伤效应。方法以Daudi细胞系作为淋巴瘤靶细胞，用^51Cr释放法分别检测18例B细胞淋巴瘤患者和13名健康成人的外周血单个核细胞（PBMNC）的直接细胞毒作用和抗体（利妥昔单抗）介导的细胞毒作用，其结果与患者经利妥昔单抗治疗后疗效进行比较。观察IL-2能否增强PBMNC的直接细胞毒作用和利妥昔单抗介导的细胞毒作用，并通过流式细胞术（FCM）检测IL-2活化前后PBMNC的细胞表型变化。结果淋巴瘤患者的PBMNC对靶细胞的直接杀伤作用和利妥昔单抗介导的细胞毒作用均较健康成人显著降低[效靶比为20：1时特异性细胞杀伤率分别为（5．80±1．16）％、（14．32±1．50）％和（14．29±1．68）％、（24．14±1．53）％]；其下降水平与患者经利妥昔单抗治疗后的临床疗效相关（r=0．781，P〈0．05）。患者的PBMNC在体外经IL-2活化后，其直接杀伤作用和利妥昔单抗介导的细胞毒效应较未经IL-2活化组明显增强[分别为（15．43±2．62）％、（35．79±2．58）％和（5．80±1．16）％、（14．32±1．50）％，t=3．35，P=0．003和t=7．17，P〈0．001]。结论通过对B细胞淋巴瘤患者PBMNC功能的体外分析，有助于预测利妥昔单抗治疗的疗效。IL-2体外可明显增强患者PBMNC的直接杀伤作用和利妥昔单抗介导的细胞毒作用。Objective To establish a method to predict therapeutic effect of Rituximab and explore the feasibility and potential of IL-2 improving antitumor activity of Rituximab with upregulated antibody-denpendent cellular cytotoxicity （ADCC） in patients with B-cell lymphoma. Methods Eighteen B-cell lymphoma patients and 13 health volunteers entered the study. Peripheral blood mononuclear cells （PBMNC） were isolated as effector cells, and Daudi （ Burkitt＇ s lymphoma） cells as target cell, the cytotoxicity and ADCC mediated by Rituximab （ 10 μg/ml） of PBMNC at different E： T ratios were performed by standard ^51Cr-re-Iease-assay in vitro with or without IL-2-activation. Flow cytometric analysis was performed to identify PBMNC phenotype with or without IL-2-activation. Results A marked decrease of cytotoxicity and Rituximab mediated ADCC in the patients as compared with that in health volunteers, the results being （5.80 ± 1.16）%,（14.32±1.50）% and （14.29±1.68）%, （24.14 ±1.53）%（t=3.693,P=0.001 and t= 3.372,P=0. 003）respectively. The decrease was correlated with the therapeutic effect of Rituximab （r = 0. 781 ,P 〈 0.05 ）. The cytotoxicity and Rituximab mediated ADCC in the patients could be partly recovered after IL-2 activation from （ 5.80 ±1.16 ） %, （ 14.32 ± 1.50 ） % to （ 15.43 ± 2.62 ） %, （ 35.79 ± 2.58 ） % （t = 3.35 ,P = 0.003 and t = 7. 17, P 〈 0.001 ） respectively. Conclusions It may be a useful method for predicting the effect of Rituximab in B-cell lymphoma patients to analyze the cytotoxicity and ADCC of their PBMNC. The impaired activity of PBMNC could be partly recovered when IL-2 was administered before the use of Rituximab.

关 键 词：淋巴瘤 非霍奇金 利妥昔单抗 抗体依赖细胞细胞毒性 白细胞介素2 

分 类 号：R686[医药卫生—骨科学]