外泌体（exosomes）是介导不同类型细胞间信号交流的重要载体，在肿瘤免疫中发挥重要的调控作用。肿瘤细胞来源的外泌体(Tumor-derived exosomes ，TDEXs)中包含多种调控肿瘤免疫的lncRNAs和miRNAs，但调控的方式和机制尚不明确。课题组前期研究表明，口腔鳞癌TDEXs作用NK细胞后，能显著影响其杀伤活性及NF-κB信号通路的激活；同时还发现，TDEXs能把口腔鳞癌中高表达的lncRNA-ENST000000470170和lncRNA-FR344886转运到NK细胞中，并发挥作用。由此推测，口腔鳞癌TDEX-lncRNAs在调控NK细胞方面，具有不同的作用和机制。本项目以口腔鳞癌TDEX-lncRNAs为研究对象，探究TDEXlncRNA-NF-κB轴在调控NK细胞杀伤活性方面的作用和机制。进一步通过对人口腔鳞癌组织样本、口腔鳞癌细胞系NOD-SCID鼠移植瘤模型、正常免疫小鼠荷瘤模型的研究，评估TDEX-lncRNAs作为口腔鳞癌诊治靶标的可行性。

Exosomes are especially important in communication between cells, which could play a vital part in the regulation of tumor immunity. Tumor-derived exosomes (TDEXs) have been reported to carry biological active molecules and signaling factors (including lncRNAs, miRNAs et al.), which are able to regulate functions of immune cells. However, the detailed mechanism remains unclear, especially in NK cell-mediated anti-cancer immunity. Our previous studies indicated that exosomes derived from oral squamous cell carcinoma (OSCC) cells can enter NK cells and regulate their cytotoxic function, which was closely associated with NF-κB signaling pathway. Moreover, the functional lncRNA-ENST000000470170 and lncRNA-FR344886, which are highly up-regulated in OSCC cells, could be transferred from OSCC cells to NK cells via exosomes. According to our previous studies, we speculate that the exosomal lncRNAs derived from OSCC cells might play a unique and important role in the regulation of NK cell cytotoxic function. In this study, we mainly focus on the mechanism of immunomodulatory mediated by the TDEX-lncRNA-NF-κB axis. The feasibility of exosomal-lncRNAs as a target for the diagnosis and treatment of OSCCs will be evaluated by further studies on OSCC samples, the OSCC cell xenograft models in NOD-SCID mice and dimmunocompetent mice. In summary, the present research will provide some valuable strategies for exosome-based oral cancer therapies in the future.