Fas配体诱导淋巴细胞凋亡与肾癌免疫攻击作用

目的　探讨Fas配体 (FasL)诱导淋巴细胞凋亡与肾癌免疫攻击作用的关系。　方法　采用免疫组化技术检测 4 4例肾癌组织FasL表达及肿瘤周围浸润淋巴细胞 (TIL)凋亡情况 ,并应用肾癌细胞株 786 0、GRC 1与JurkatT淋巴细胞共培养检测T细胞凋亡率。SP法检测Ki6 7表达 ,评价肾癌预后。　结果　 (1) 4 4例肾癌组织FasL表达阳性率 4 6 .5 % ,高于正常肾组织的 2 3.2 % ,差别有显著性意义 (P <0 .0 1)。随肾癌分期增加 ,FasL表达阳性率增加。肾癌FasL表达率与Ki6 7表达率呈显著正相关 (r =0 .93,P <0 .0 1)。 (2 )肾癌组织TIL凋亡率为 33.9% ,高于正常肾组织的3.5 % ,差别有显著性意义 (P <0 .0 1)。肾癌FasL表达率与TIL凋亡率呈显著正相关 (r =0 .96 ,P <0 .0 1)。 (3) 786 0FasL表达率 18.6 % ,GRC 1表达率 2 .3% ,二者差别有显著性意义 (P <0 .0 1)。Ju rkat细胞与 786 0细胞共培养的凋亡率 14 .9% ,与GRC 1共培养的凋亡率 1.3% ,二者差别有显著性意义 (P <0 .0 1)。中和抗体NOK 2中和 786 0细胞FasL后 ,与之共培养的Jurkat细胞凋亡率显著减少 (P <0 .0 1)。　结论　肾癌组织FasL表达增高 ,以此诱导淋巴细胞凋亡 ,实现对宿主的免疫攻击。

Role of FasL in affecting immune system of the host in renal cell carcinoma

Objective To investigate the mechanism of renal cell carcinoma (RCC) in affecting the immune system of the host. Methods FasL expression and the apoptosis of tumor infiltrating lymphocytes (TIL) were examined by immunohistochemical technique in 44 cases of RCC.FasL function was assessed by coculture assays in vitro using the renal cancer cells 786 0 or GRC 1 and the Fas sensitive Jurkat T cells. Results (1)FasL expression rate in RCC (46.5%) was higher than that in the normal kidney tissues (23.2%, P <0.01). The expression rate of FasL in RCC was significantly increased correlating with RCC stage ( P <0.01). The expression of FasL with Ki67 had a positive correlation ( r= 0.93,P <0.01).(2)The apoptotic rate of TIL in RCC (33.9%) was significantly higher than that of the normal kidney tissues (3.5%, P <0.01).The expression of FasL and the apoptotic rate of TIL in RCC had a positive correlation with each other ( r=0.96,P <0.01).(3)The FasL expression rate of 786 0 (18.6%) was higher than that of GRC 1 (2.3%, P <0.01). FasL expressed by 786 0 cells could induce apoptosis of Jurkat T cells in coculture assays and apoptosis of Jurkat T cells was significantly decreased after blocking the effect of FasL with Fas neutralizing antibody NOK 2,the apoptotic rates being 14.9% and 2.0% respectively ( P <0.01).The apoptotic rate of Jurkat T cells cocultured with GRC 1 was 1.3%,being significantly lower than that of Jurkat T cells cocultured with 786 0 ( P < 0.01 ). Conclusions FasL expressed by renal cancer cells could induce T cell apoptosis,playing a cardinal role in affecting the immune system of the host.