EB病毒潜伏期蛋白LMP1与免疫分子41BBL的相互作用关系在鼻咽癌发病及治疗中的功能机制及临床意义研究

鼻咽癌是一种高发于我国的头颈部恶性肿瘤。EB病毒与鼻咽癌密切相关，其中EB病毒中重要的潜伏蛋白LMP1是目前被认为与鼻咽癌发生发展最密切的病毒蛋白之一，为了进一步探索LMP1在鼻咽癌发生发展中的机制，我们使用串联亲和纯化的方法联合质谱分析，发现了免疫共刺激因子41BBL。41BBL是参与免疫细胞激活的重要因子，在淋巴瘤的机制研究中发现通过与EB病毒LMP1的相互作用参与了淋巴瘤的发生发展过程。同时，41BB/41BBL也是目前备受关注的免疫治疗靶点之一，目前尚无41BBL与鼻咽癌相关相关机制的研究。本项目拟从蛋白结合、细胞功能实验、免疫机制研究、临床数据分析等方面了解LMP1与41BBL的相互作用关系以及所带来的细胞生物学效应，机体免疫效应与肿瘤发生发展新机制。本项目的开展有利于揭示鼻咽癌发病及治疗中的潜在机制，发现新的免疫调控机制，也为鼻咽癌治疗以及预后分析提供新的思路。

Nasopharyngeal carcinoma (NPC) is the malignancy in head and neck, which mainly exists in southern China. EBV plays an important role in development of nasopharyngeal carcinoma, and EBV latent protein LMP1 contributes to NPC development according to previous research, which is involved in various stages of the tumorigenesis process. In order to clarify the role of LMP1 in NPC development and uncover new mechanism of tumorigenesis, especially in immune activation and immune escape processes. We used tandem affinity purification to find the potential interaction protein, and based on the mass spectrum results, we found immune co-stimulating factor 41BBL, which is an important factor involved in immune activation, and one of the most concerned immune treatment targets at present. This project is intended to discover the influence induced by interaction between LMP1 and 41BBL with cell function experiment, immunological experiment and clinical data analysis, and find out new mechanism in NPC occurrence, development and treatment. This project is helpful to reveal the potential mechanism between EBV and T cells of nasopharyngeal carcinoma, and hopefully to find a new immune regulation mechanism, which may help us to improve the understanding of NPC.