细胞因子IFNα等在肾癌免疫治疗中的作用

Effect of Interleukin-2,interferon-α and tumor necrosis factor-α on the immunological therapy for renal cell carcinoma

目的 研究 IL 2、IFNα、TNFα对肾癌 Fas蛋白表达影响并进一步探讨它们在肾癌免疫治疗中的作用。方法 采用免疫组化方法分析 4 4例肾细胞癌标本及相邻正常肾组织 Fas蛋白表达情况 ;体外培养 786 - 0肾癌细胞株 ,流式细胞仪 (FCM)分析肾癌细胞 Fas表达及凋亡。结果 肾癌组织 Fas阳性表达率 (2 2 .8%)显著低于正常肾组织中 Fas的表达 (5 3.8%) ;IFNα能刺激肾癌细胞 Fas的表达并增强抗 Fas抗体 (CH1 1 )对肾癌细胞的细胞毒效应 ,IL 2、TNFα并不能刺激肾癌细胞 Fas的表达 ,也不能增强抗 Fas抗体 (CH1 1 )对肾癌细胞的细胞毒效应。结论 肾癌细胞低表达 Fas是其逃避机体免疫攻击的原因之一 ;肾癌细胞表达一定水平有功能的 Fas是 CH1 1发挥细胞毒效应的前提。

Objective To study the influence of interleukin-2(IL2),interferon-α(IFNα) and tumor necrosis factor-α(TNFα) on Fas expression and the immunological therapy for renal cell carcinoma. Methods The expression of Fas protein in 44 cases of renal cell carcinoma and 10 cases of normal kidney tissue was assayed by means of immunohistochemical VP technique. Fas expression and cell apoptosis in cultured 786-0 renal cell carcinoma cells were detected by the flow cytometry. Results Fas expression rate in renal cell carcinoma tissues (22.8%)was significantly lower than that in normal kidney tissues(53.8%,P<0 01). IFNαcould enhance the expression of Fas and promote the cytotoxic effect of CH11 on renal cell carcinoma cell; while IL2 and TNFαcould not. Pretreatment of 786-0 renal cell carcinoma cell line with IL2 in combination with IFNαor IFNαtogether with TNFαcould augment the Fas expression and Fas-mediated cell apoptosis. Conclusion The lower Fas expression may be one of immune escape mechanisms in renal cell carcinoma. Cytotoxic effect of CH11 on renal cell carcinoma must rely upon renal cell carcinoma cell to express functionally a certain level of Fas.