免疫学治疗已成为继手术、放疗和化疗后的第四种肿瘤治疗方法，而免疫抑制分子B7-H1在肝癌细胞高表达所引发的肝癌免疫逃逸，是有效免疫治疗的一大障碍。但是其高达的原因和机制至今未明。为解释B7-H1在肝癌细胞高表达的原因，本项目在前期研究工作基础上，首次提出肿瘤相关巨噬细胞诱导肝癌细胞高表达B7-H1分子,进而介导免疫逃逸的新观点，拟通过临床标本检测、细胞学和动物学实验加以科学论证，从而揭示这一炎症促肿瘤新机制，丰富肿瘤免疫学理论；为探讨B7-H1在肝癌细胞高表达的机制，本项目避繁就简，从增强体这一表达调控关键因素着手，拟首次研究肿瘤相关巨噬细胞诱导肝癌细胞高表达B7-H1的特定增强体组成和作用模式，这可为阻断B7-H1的诱导表达提供直接并特异的新靶点和新策略，是开发新型药物以抑制免疫逃逸，提高免疫治疗效果的前提和基础。

High mortality rate of human hepatocellular carcinoma (HCC) is attributed to its recurrence and metastasis after surgery. Immunotherapy based on CTL cells is a prospective treatment to eradicate the residual malignant cells after surgery, but it is impaired by immune escape of HCC. One of important mechanism of immune escape is the overexpression of B7-H1 on HCC cells since the B7-H1 can bind to its receptor PD-1 existing on CTL cells to lead them to apoptosis. However, it is not well known so far why and how the B7-H1 is expressed in HCC cells. Why is the B7-H1 overexpressed in HCC cells? Our preliminary study implied that the overexpression of B7-H1 in HCC cells might be due to inflammatory microenvironment predominated by tumor associated macrophages (TAM). We found that overexpression of B7-H1 in malignant cells was associated with macrophages infiltration in HCC tissues. In addition, The B7-H1 expression in HCC cell lines was upregulated by macrophages in a transwell coculture system. Based on these results, we put forward a novel hypothesis that TAM induces overexpression of B7-H1 in HCC cells via producing multiple inflammatory cytokines. In this project, we are going to analyze clinical samples and design cytological experiments and zoological experiments to further reveal the mechanism of B7-H1 overexpression in HCC.The anticipated results will provide new knowledge for tumor immunology. How is the B7-H1 overexpression induced by TAM? We assume that a specific enhanceosome control the induction of B7-H1 overexpression.In this project, we are also going to analyze the composition and action mode of the enhanceosome. Enhancesome is a complex located on the gene promoter region, composed of multiple transcription factors activated by signaling from the outside of the cell. The B7-H1 enhanceosome can control the B7-H1 expression more directly and specificly than the inflammatory cytokines and signaling pathways. It will be the first time to describe the B7-H1 enhanceosome.Moreover, the study will provide new targets and strategies for new medicine-design and inhibition of immune escape. Based on our preliminary study and the theory of enhanceosome, we propose our hypothesis that TAM induces the overexpression of B7-H1 on HCC cells through a specific enhanceosome mechanism. In this project, we will give an answer to why and how the B7-H1 is overexpressed in HCC cells. All the results from this project will pave a way to block immune escape and improve immunotherapy of HCC.