肿瘤细胞TLR9介导自噬的分子机制及其对CpG ODN免疫治疗作用研究

TLR9 plays a critical role in innate host defense as well as in initiation of adaptive immune responses, however, the biological function of TLR9 expressed by tumor cells was poorly studied. Recently, we observed that CpG ODN, the ligand of TLR9, could induce tumor cells autophagy in vitro. So far, the molecular mechanisms of tumor cells autophagy induced by TLR9 have not been studied before. In this project, as the first step, we will confirm tumor cells autophagy can be induced by TLR9 activation both in vitro and vivo. Then, potential cross-talk between TLR9 and autophagy pathway will be studied by western blot and co-immunoprecipitation. Furthermore, we will clarify the effects of autophagy induced by TLR9 on CpG ODN-based immunotherapy by animal experiments. Results of this project will provide solid evidence to clarify potential connection of TLR9 and autophagy pathway, and to develop novel immunotherapy for tumor.

TLR9在宿主天然防御和继发免疫反应中发挥重要作用，既往研究多关注于免疫细胞TLR9的生物学功能，但对肿瘤细胞TLR9信号通路的作用研究较少。课题组前期研究中发现，TLR9的配体CpG ODN能在体外诱导肿瘤细胞自噬。目前TLR9介导自噬的分子机制尚无研究。本研究拟首先验证TLR9信号通路激活在体内外对肿瘤细胞自噬的介导作用。随后，通过western blot和免疫共沉淀等技术研究TLR9和自噬信号通路潜在的cross-talk。本研究将进一步通过动物实验，阐明肿瘤细胞TLR9介导自噬是否对CpG ODN免疫治疗产生影响。本研究将为揭示免疫调节TLR9信号通路和参与细胞代谢和应激的自噬信号通路的潜在联系，为进一步研究肿瘤免疫治疗方案提供基础。