癌相关成纤维细胞（cancer-associated fibroblasts，CAFs）是口腔癌微环境的重要组分之一，在肿瘤免疫中发挥重要的调控功能。作为细胞间信息交流的重要载体，外泌体（exosomes，Exos）在CAFs与免疫细胞互作过程中发挥着重要作用，但具体作用机制尚不明确。课题组前期研究表明，口腔癌CAF-Exos显著抑制NK细胞的杀伤活性和MAPK/ERK通路的激活；同时，口腔癌CAF-Exos表面富含的B7H3蛋白与CAF-Exos介导的NK细胞杀伤活性的下调相关。由此推测，口腔癌CAFs来源Exo-B7H3具有调控NK细胞活性的作用。本项目以口腔癌CAFs来源Exo-B7H3为研究对象，探究CAF-Exo-B7H3通过MAPK/ERK通路抑制NK细胞杀伤活性的作用和机制。进一步通过对血清外泌体样本及荷瘤小鼠模型的研究，对Exo-B7H3作为口腔癌诊治靶标的可行性进行分析。

Cancer-associated fibroblasts (CAFs) are one of the important components of oral cancer microenvironment, which play an important regulatory role in tumor immunity. As an especially important carrier of cellular communication, exosomes (Exos) play a vital part in the process of interaction between CAFs and immune cells. However, the detailed mechanism remains unclear, especially in NK cell-mediated anti-cancer immunity. Our previous studies revealed that CAF-derived exosomes (CAF-Exos) can inhibit the cytotoxicity of NK cells, which was closely associated with inhibition of MAPK/ERK signaling pathway. Moreover, it was found that the surface of CAF-Exos was rich in B7H3 protein, which was related to the down-regulation of cytotoxic function of NK cells mediated by CAF-Exos. According to our previous studies, we speculate that the exosomal B7H3 derived from CAFs might regulate the functional activity of NK cells. In this study, Exo-B7H3 of CAFs is selected as the research object and we mainly focus on the mechanism of immunomodulatory mediated by CAF-Exo-B7H3 via MAPK/ERK signaling pathway in NK cells. The feasibility of CAF-derived exosomal B7H3 as a target for the diagnosis and treatment of oral cancer will be evaluated by further studies on serum exosomes from oral cancer patients and the xenograft models. In summary, the present research will provide some valuable strategies for exosome-based cancer therapies in the future.