TLR7配体Imiquimod促进胶质瘤干细胞自我更新的作用及机制研究

胶质瘤干细胞（GSC）具有强大的自我更新、增殖和分化能力，是恶性胶质瘤发生、发展及维持的罪魁祸首，更是术后复发的主要原因。目前发现Toll-like Receptor（TLR）家族成员在某些肿瘤发生发展中起重要作用，但在GSC中的研究尚未报道。本项目组前期研究发现体外无血清培养的GSC高表达TLR7，其配体Imiquimod（IMQ）可以促进GSC自我更新，同时IMQ刺激后培养上清中检测到了高水平IL-6。结合肿瘤炎性微环境与肿瘤发生发展的研究，我们推测IMQ可能通过激活TLR7信号通路，诱导分泌促炎性细胞因子，从而促进GSC的自我更新与增殖。本课题将对这一假设进行研究，并对该过程中相关信号转导途径的参与机制进行初步探讨。 本课题的完成将揭示TLR7信号通路与GSC自我更新的内在联系，为恶性胶质瘤的复发找到新的可能原因，同时为发掘新的GSC干预治疗靶标提供理论依据。

Glioma stem cells (GSC) have strong ability of self-renewal, proliferation and differentiation, and play an important role in the development and recurrence of malignant glioma. Several studies identified that the Toll-like receptor (TLR) family as critical players in the occurrence and development of certain tumors, which have not been reported in GSC. Our preliminary study found that Toll-like receptor 7 (TLR7) is highly expressed in GSC, and tumor sphere-forming ability of GSC can be promoted by TLR7 agonist, Imiquimod (IMQ ).Interstingly, GSC cells showed substantially increased secretion of interleukin 6 (IL-6). Combining with the investigation of inflammatory microenvironment in tumor progression, we speculate that self-renewal ability of GSC may be regulated by TLR 7 mediated signaling via induction of proinflammatory cytokines. According to our previous, we intend to adopt the GSC derived from glioma cell lines and glioma patients as the research objects, identify the regulatory mechanism of promoting of GSC self-renewal after stimulation of TLR7 agonist, and the role of IMQ through the method of immunology and molecular biology. This will lead to new targets in the treatment of malignant glioma.