Cancer Immunotherapy Targeting B7-DC/ B7-H1/ PD-1 interaction May Improve Tumor Microenviroment

B7-H1是调节在免疫效应细胞和癌症的两个亚群上表达的免疫检查点的共信号。B7-H1能够通过PD-1受体诱导CD 8 + T细胞的无反应性，导致肿瘤生长和免疫抑制。用中和抗体阻断B7-H1是一种改变肿瘤微环境的新疗法。这种B7-H1/ PD-1相互作用的抗体阻断可能导致免疫应答和肿瘤微环境的改变，从而防止肿瘤逃避免疫系统。材料和方法：BALB/ C小鼠用结肠直肠肝转移攻击，然后用减毒单核细胞增生李斯特菌（LM）疫苗平台联合B7-H1阻断抗体治疗。结果：B7-H1+ LM组小鼠存活率为70%。免疫亚群的分析表明，用LM处理的小鼠的CD 8 + T细胞上的B7-H1表达增加。体外CD 8 + T细胞活化分析显示，在肿瘤存在的情况下，B7-H1阻断抗体使CD 8 + T细胞活化增加了50%。

B7-H1 is a co-signal to modulate immune check point expressed on both subsets of immune effector cells and cancer. B7-H1 is able to induce an anergy of CD8+ T cells through the PD-1 receptor leading to tumor growth and immune suppression. Blockade of B7-H1 with neutralizing antibody is a novel therapy which alters tumor microenvironment. The antibody blockade of this B7-H1/ PD-1 interaction may result in the alteration of immune response and tumor microenvironment preventing tumor evasion from the immune system. Materials and Methods:BALB/ C mice were challenged with colorectal hepatic metastases and then treated with an attenuated Listeria monocytogenes(LM) vaccine platform in combination with B7-H1 blocking antibody. Mice were investigated for survival, immunological analysis with flow cytometry and in vitro assayResults : Mice treated with B7-H1+ LM had 70% survival. The analysis of immune subsets demonstrated an increase in expression of B7-H1 on CD8+ T cells of mice treated with LM. In vitro analysis of CD8+ T cell activation showed an increase of 50% in the presence of tumor with B7-H1 blocking antibody.Discussion : B7-H1 blockade showed increased survival by preventing the inhibitory signaling between T cells, dendritic cells and tumor.