成纤细胞维激活蛋白是诱导肿瘤微环境免疫逃逸的关键分子，但诱导机制尚未阐明。我们前期研究表明，FAP+成纤维细胞能刺激肿瘤高表达TGFβ，并且与肿瘤共培养上清能诱导PBMCs向Treg细胞分化。分析发现FAP可能作为信号分子与其功能受体结合并激活STAT3/TGFβ信号通路。因此，筛选FAP的功能受体和研究其介导的信号通路成为本项目的核心科学问题。本研究拟通过免疫共沉淀和质谱等手段锁定FAP在肿瘤细胞上的功能受体。通过Gain-and loss of function策略，利用定量PCR和免疫印迹等技术在FAP、功能受体和STAT3/TGFβ三个层次上对该通路进行全面系统地研究和验证。最后，在体内外探讨FAP在肿瘤微环境中的免疫抑制效应，以期阐明FAP通过结合其功能受体激活STAT3/TGFβ信号通路诱导肿瘤微环境免疫逃逸的机理。本研究不仅为肿瘤的防治提供新靶点，也开辟了FAP研究的新方向。

Fibroblast activation protein (FAP) is a key molecule of the induction of local immune suppression in tumor microenvironment. Based on the previous study, we found that FAP+ fibroblast cells could upregulate the TGF-β expression in tumor cells, and the supernant from co-culture of FAP+ fibroblast cells and tumor cells could stimulate the differentiation of mice PBMC to Treg. The systemic analysis of the results implicated that STAT3/TGF-β signaling pathway may be the key event of the induction of immune escape. Therefore, to exploration the functional receptor of FAP and its signaling pathway is the significant scientific question of this program. In this study, we intend to identify the functional receptor of FAP in tumor cell by employing immune precipitation and mass spectrum. We also investigate the regulation network among FAP, functional receptor and STAT3/TGF-β by using qRT-PCR and Western blot adopting gain-and loss of function strategy. Finally, the immune suppressive effect of FAP in tumor microenvironment will be validated both in vitro and in vivo to elucidate the mechanism of FAP mediated immune escape in tumor microenvironment from STAT3/TGF-β signaling pathway. The study will not only indicate new target and new theory in tumor treatment and prevention, but also open up new study direction of FAP.