研究表明，肿瘤相关成纤维细胞(CAFs)通过肿瘤代谢的自噬性间质偶联在肿瘤的发生发展中起着重要作用。同时，exosome作为一种新的旁分泌途径参与了肿瘤微环境中的信号传递。我们前期的研究工作初步发现，肿瘤细胞中的致瘤蛋白LMP1可以通过exosome途径进入成纤维细胞(NFs),促使NFs活化为CAFs,并与肿瘤细胞的放射抵抗相关。在此基础上，本课题将以LMP1阳性的鼻咽癌为研究模型，从CAFs活化的角度，在体内外水平,系统研究exosome负载的LMP1是否通过NF-κB信号促进NFs向CAFs的活化，以及CAFs是否通过肿瘤代谢的自噬性间质偶联机制诱导肿瘤放射抵抗。本研究从一个新的角度来认识致瘤蛋白LMP1参与肿瘤放射抵抗的途径和机制，为EBV相关肿瘤的靶向治疗提供了新的启示。

Research shows that cancer associated fibroblasts (CAFs) play the crucial role in tumorigenesis through coupling mechanism between autophagic-stroma and tumor metabolism. Recently, exosome has been regarded as a new paracrine pathway involving in signal transduction of tumor microenvironment. In our previous study, it was found that latent membrane protein1 (LMP1) in tumor cells could be transfered into normal fibroblasts (NFs) via exosome and stimulate the activation of NFs to CAFs, which lead to radioresistance of tumor cells. Based on the above, by using nasopharyngeal carcinoma with positive LMP1 as a model system, from the point of view of CAFs activation, we will evaluate whether and how LMP1 harbored by exosome promotes fibroblast activiation to CAFs in tumor microenvironment in vivo and in vitro. We will also discuss whether CAFs induce tumor radioresistance through coupling mechanism between autophagic-stroma and tumor metabolism in this project. In a word, this study will enhance our understanding on the mechanism of LMP1 involving in radioresistance of tumor cells in a new perspective, and provide us important molecular targets for EBV-related tumor therapy.