肾癌Fas和FasL蛋白表达异常对其免疫逃避机制的影响

目的探讨肾癌系统表达异常对其免疫逃避机制的影响。方法采用免疫组化方法分析44例肾癌组织及相邻正常肾组织Fas、FasL表达情况;用TUNEL法检测44例肾癌标本中浸润性T淋巴细胞的凋亡。体外培养786-0肾癌细胞株,流式细胞仪(FCM)分析肾癌细胞株Fas、FasL的表达及肿瘤细胞的凋亡;体外培养Fas+的Jurkat细胞,FCM检测其凋亡情况。结果肾癌细胞Fas表达率为22.8%,显著低于其在正常肾组织中表达率(53.8%,P<0.01)。而FasL表达率(46.5%)显著高于其在相邻正常肾组织在的表达(23.2%)。肾癌组织Fas、FasL表达呈负相关(r=-0.46,P<0.05);肾癌浸润性T淋巴细胞凋亡率(33.1%)与肾癌FasL表达呈正相关(r=0.96,P<0.01)。化疗药物5-Fu能上调肾癌细胞株786-0Fas的表达,并增强肾癌细胞对Fas抗体的细胞毒效应,通过抑制肾癌细胞株786-0FasL表达而降低其攻击JurkatT淋巴细胞的能力。讨论肾癌细胞免疫逃避机制包括两方面:一方面通过Fas低表达,能逃避Fas单克隆抗体介导的凋亡;另一方面通过FasL高表达,具有主动攻击免疫淋巴细胞的能力。临床化疗药物5-Fu就Fas系统而言通过上调Fas、抑制FasL的表达发挥一定的疗效。

The Effect of Fas and FasL Abnormal Expression on Immune Escape Mechanism of Renal Cell Carcinoma

Objective To investigate the effect of Fas and FasL abnormal expression on immune escape mechanism of renal cell carcinoma(RCC). Methods The expression of Fas and FasL was detected in 44 cases of RCC and 10 cases of normal kidney tissue by immunohistochemical method. Tumor infiltrating T lymphocyte's apoptosis in 44 cases of RCC was examined by TUNEL assay. FCM was used to detect the expression of Fas and FasL as well as apoptosis in RCC cell line 786-0. In addition, the apoptosis of Jurkat T cell with Fas exprssion was also analysed with FCM. Results Fas expression rate (22.8%) in RCC was significantly lower than that (53.8%) in normal kidney tissue(P<0.01), while FasL expression rate (46.5%) in RCC was significantly higher than that (23.5%) in normal kidney tissue. The negative correlation between Fas and FasL expression was found in RCC(r=-0.46,P<0.05), and the apoptotic rate of tumor infiltrating T lymphocyte was positively associated with FasL expression in RCC(r=0.96,P<0.01). Chemotherapeutic drug 5-Fu could increase the cytotoxic effect of anti-Fas mAb(CH11) on RCC cell line 786-0 by up-regulating Fas expression, and decrease the cytotoxic effect of RCC cell line 786-0 on Jurkat T lymphocyte by down-regulating FasL expression. Conclusion Immune escape mechanism of RCC included escaping the cytotoxic effect of anti-Fas mAb by down-regulating Fas expression, and enhancing its ability for attacking T lymphocyte by up-regulating FasL expression. Chemotherapeutic drug 5-Fu had a certain therapeutic effect on RCC by increasing Fas expression and decreasing the FasL expression in RCC.