阻断B7-H1通路增强膀胱癌患者外周血树突状细胞免疫功能的实验研究

Experimental study on enhancement of immune function of dendritic cells from peripheral blood of patients with bladder cancer by blocking the B7-H1 pathway

目的:探讨膀胱癌患者外周血与正常人外周血树突状细胞(DCs)免疫功能的差异以及B7-H1阻断对膀胱癌患者外周血DCs免疫功能的影响。方法:采集膀胱癌患者及正常人的外周血,用rhGM-CSF、rhIL-4和rhTNF-α自外周血单个核细胞(PBMC)诱导分离DCs,混合淋巴细胞反应检测DCs刺激淋巴细胞增殖的能力。然后于膀胱癌DCs组加入B7-H1的阻断型抗体,混合淋巴细胞反应检测B7-H1阻断后DCs刺激淋巴细胞增殖的能力,ELISA法检测阻断后DCs分泌IL-10和IL-12的水平。结果:膀胱癌患者外周血DCs刺激淋巴细胞增殖的能力低于正常人外周血DCs,而加入B7-H1阻断型抗体阻断B7-H1后,膀胱癌患者外周血DCs刺激淋巴细胞增殖的能力得到明显提高,同时其分泌IL-10水平明显降低,而分泌IL-12水平明显增加。结论:膀胱癌患者外周血DCs存在免疫功能缺陷,其机制可能与DCs表面B7-H1的诱导高表达有关,而B7-H1阻断能够增强膀胱癌患者外周血DCs的免疫功能。

Objective： To explore the differences of dendritic cells （DCs） in peripheral blood between patients with bladder cancer and normal human, and to investigate the effects of B7-H1 blockade on the immune function of DCs in peripheral blood of patients with bladder cancer. Method： DCs were induced by stimulation of patients with bladder cancer and normal human peripheral blood mononuclear cells （PBMC） with rhGM-CSF, rhIL-4 and rhT- NF-a. Then the DCs in peripheral blood of patients with bladder cancer were cultured with anti-B7-H1 mAbs to block B7-H1 pathway. The proliferation efficiency of DCs was measured by mixed lymphocyte reaction and the concentration of IL-10 and IL-12 were measured by ELISA method. Result： The proliferation efficiency of DCs was lower in patient group than in healthy group. Blockade of BT-H1 promoted the proliferation of DCs and enhanced iL-12 secretion but suppressed IL-10 secretion. Conclusion： Immune dysfunction exists in DCs in peripheral blood of patients with bladder cancer. The mechanism may be associated with high expression of B7-H1 on circulating DCs, whereas blockade of B7-H1 can enhance immune function of DCs in peripheral blood of patients with bladder cancer.