基于NFkB-cGAMP-cGAS-STING通路研究树突状细胞在鼻咽癌放疗免疫致敏中的作用

放疗是鼻咽癌的主要治疗手段，复发和转移为常见治疗失败的原因。现已知道，放疗诱导的机体免疫应答类型与临床预后密切相关。而作为机体内功能最为强大的抗原提呈细胞-树突状细胞（dendritic cells, DCs）在其中的作用并不清楚。我们的前期工作发现，鼻咽癌患者的外周血和肿瘤组织中的一些淋巴细胞和DCs亚群的数量在放化疗后发生了显著变化，经不同剂量射线照射的鼻咽癌细胞发生免疫原性细胞死亡，并且能显著上调DCs的免疫表型分子的表达水平。基于此，提出以下科学假设：放疗诱导的鼻咽癌细胞免疫原性细胞死亡在DCs的介导下发挥免疫调节作用。因此，本项目拟从分子、细胞、动物和临床水平研究经不同剂量射线照射后的鼻咽癌细胞对DCs免疫学功能的影响及其诱导的免疫应答类型和分子机制，筛查潜在的肿瘤特异性抗原或肿瘤相关抗原，构建数学模型模拟该过程，以期深入理解DCs的免疫功能，为鼻咽癌的临床治疗模式提供理论指导。

Radiotherapy is the main treatment for nasopharyngeal carcinoma (NPC), recurrence and metastasis are the common causes of treatment failure. It has been known that the type of immune response induced by radiotherapy is closely related to the clinical prognosis. However, as the most powerful antigen presenting cells in the body, the role of dendritic cells (DCs) in this process is not clear. In our previous work, we found that the numbers of lymphocytes and DCs subsets in NPC patients changed significantly after radiotherapy and chemotherapy. NPC cells exposed to different doses of radiation resulted in immunogenic cell death and significantly increased the expression levels of immune phenotype molecules in DCs. On this basis, we propose the following scientific hypothesis: radiation-induced NPC immunogenic cell death plays an immunomodulatory role under the guidance of DCs. Therefore, this project will study the influence of NPC cells irradiated by different doses of radiation on the immunological function of DCs and the resulting immune response types as wells as potential molecular mechanisms, screening potential tumor specific antigen/tumor associated antigen or neoantigen at the levels of molecule, cell, animal and clinic by the methods of omics and immunology, and building a mathematical model to simulate the process, in order to understand the immunoregulatory function of DCs and provide theoretical guidance for the clinical treatment of NPC.