膀胱移行细胞癌组织中B7-H1和PTEN的表达及意义

目的探讨共刺激分子B7-H1和PTEN在膀胱移行细胞癌组织中的表达变化及意义。方法采用免疫组化SP法检测50例膀胱移行细胞癌及10例正常膀胱组织中的B7-H1和PTEN,分析其与膀胱移行细胞癌临床病理参数的关系及两者的相关性。结果正常膀胱组织中B7-H1不表达,膀胱移行细胞癌组织中B7-H1的阳性表达率为72%,且B7-H1的表达与肿瘤的病理分级、临床分期及复发密切相关（P〈0.05）;正常膀胱组织中PTEN呈阳性表达,膀胱移行细胞癌中PTEN蛋白阳性表达率为58%,随着肿瘤病理分级、临床分期的增加PTEN表达显著降低（P〈0.05）。B7-H1与PTEN的表达呈明显负相关（r=-0.44,P〈0.01）。结论膀胱移行细胞癌中B7-H1的高表达和PTEN的突变或缺失与肿瘤的发生发展和免疫逃逸密切相关。     

阻断B7-H1通路增强淋巴细胞抗膀胱肿瘤免疫效应的研究

B7-H1是共刺激分子B7家族的新成员,其与受体结合后可以诱导特异性T细胞凋亡,是近年来发现与淋巴细胞活化调控和肿瘤免疫逃逸现象有关的重要分子之一.我们采用B7-H1阻断型抗体阻断活化T细胞表面B7-H1的表达,进而检测B7-H1阻断对淋巴细胞的增殖能力、分泌细胞因子水平以及体外抗膀胱肿瘤免疫效应的影响.     

Costimulatory molecule B7-H1 on the immune escape of bladder cancer and its clinical significance

B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were con- structed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence （P〈0.05）. The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.     

B7-H1阻断对CD3AK细胞体外生物学活性的影响

目的: 探讨B7-H1阻断对CD3AK细胞增殖活化及其抗肿瘤免疫效应的影响.方法: 利用CD3单克隆抗体(mAb)刺激健康人外周血淋巴细胞诱导产生CD3AK细胞,然后利用B7-H1阻断型抗体阻断B7-H1通路,3H-TdR渗入法检测阻断后CD3AK细胞的增殖能力,ELISA法检测阻断后CD3AK细胞分泌IFN-γ、 TNF-α和IL-10的水平,同时将CD3AK细胞作用于膀胱肿瘤BIU-87细胞,MTT法检测阻断后CD3AK细胞的杀伤活性.结果: B7-H1阻断后,CD3AK细胞的增殖能力明显增强,体外存活时间明显延长;其分泌IFN-γ、 TNF-α的水平明显提高,而分泌IL-10的水平明显下降;同时CD3AK细胞对BIU-87细胞的杀伤活性亦明显升高.结论: 阻断B7-H1通路可以促进和维持CD3AK细胞的增殖和活化,并增强其抗肿瘤的免疫效应.阻断B7-H1通路将有望成为肿瘤免疫治疗的新策略.