作为“种子”细胞，肿瘤干细胞（CSC）在转移复发中扮演重要角色；肿瘤免疫微环境则为CSC提供良好生长环境，两者关系密切。当前CSC研究多着重于其本身，忽视肿瘤免疫微环境在其生存调控、表型维持和分化等方面的重要作用。免疫微环境和CSC作为整体进行研究有利于转移复发新机制及其防治新策略的发现。本项目在大量前期工作基础上，建立共培养体系，探讨肝癌浸润免疫细胞对CSC干性维持和促转移的作用及机制；利用分泌蛋白组学技术，筛选外周循环中调控循环肿瘤干细胞（CCSC）的免疫微环境分泌蛋白，研究其在循环系统内对CCSC功能和转移能力的影响和机制。进一步利用动物模型，阐明髓源性细胞在肝癌CSC肺转移及预转移小巢形成中的重要作用及机制。本研究将揭示肝癌免疫微环境调变CSC生物功能在肝癌转移复发中的作用和相关机制，奠定通过遏制促CSC免疫微环境进而抑制转移复发的理论和实验基础，为肝癌转移复发防治提供新思路和新靶

Cancer stem cells (CSC) are the “seeds” initiating metastasis/recurrence in cancers. Tumor microenvironment provides a niche for CSC sustainence. Currently, most CSC study focused on the intrinsic molecular mechanism and biological behavior itself, neglecting the critical impact of tumor microenvironment on the stemness maintence of CSC and its invasion and metastasis ability. Investigating the crosstalk between CSC and microenvironment may facilitate discovery of novel mechanisms of cancer metastasis and recurrence. This project will focus on several stromal cells especially immune cells in hepatocellular carcinoma (HCC) microenvironment to investigate that how tumor infiltrating immune cells regulate CSC’s stemness properties and metastatic ability, revealing the underlying molecular mechanism. Using secretome detection technologies, screening the secreting factors in peripheral blood which regulate the functions of circulating cancer stem cell (CCSC), and delineating the underlying molecular mechanism. Elucidate the vital role and molecular mechanism of bone marrow derived cells (BMDCs) in the lung metastasis process mediated by CSC and the formation of pre-metastatic niche. This study will reveal the role and mechanism of crosstalk between CSC and microenvironment in the process of metastasis/recurrence in HCC, establish the theory and experiment foundations for immune microenvironment promoted metastasis. This study may offer new intervention strategies and therapeutic target for preventing metastasis and recurrence in HCC.