泽漆汤减少肿瘤微环境中S100A9调控G-MDSC细胞亚群抑制肺癌的分子机制研究

髓源抑制细胞（MDSC）是肿瘤微环境中对T细胞具有免疫抑制特性的异质细胞群，介导肿瘤免疫逃逸。中医经方泽漆汤在临床上对肺癌有明确疗效，但其作用机制不明。本课题组前期研究发现泽漆汤可延长肺癌原位模型小鼠生存期，下调小鼠体内G-MDSC细胞亚群数量及与STAT3通路相关的S100A9基因，增加CD8+T细胞浸润，但体外泽漆汤对肺癌细胞、MDSC及T细胞并没有直接抑制或促进增殖作用。据此提出“泽漆汤下调肿瘤微环境中S100A9抑制G-MDSC细胞亚群，从而增强CD8+T细胞杀伤活性重塑肿瘤微环境抑制肺癌细胞生长”的科学假说（图1.1）。为验证假说，本课题将围绕：1泽漆汤整体抑瘤效果分析；2泽漆汤是否以G-MDSC为作用靶点发挥抑瘤功效；3泽漆汤通过下调肿瘤微环境中S100A9以抑制G-MDSC的分子机制，拟采用分子生物、分子免疫学等技术来揭示泽漆汤抑瘤功效机理，为其临床治疗肺癌提供现代科学支持。

Myeloid-derived suppressor cells (MDSC) are heterogeneous cell populations, which play immune suppressive properties for T cells,mediating tumor immune escape. Classic traditional Chinese medicine formula Ze-Qi-Tang has definite curative effect on lung cancer . However, the molecular mechanism of inhibitive effect of Ze-Qi-Tang on lung cancer has remained unknown. Our previous research showed the survival carve of orthotopic lung cancer model mice could be significantly prolonged by Ze-Qi-Tang. Moreover,the subpopulation of G-MDSC and S100A9 gene (associating with STAT3 signaling pathway) were both down-regulated by Ze-Qi-Tang. Besides, the proliferation of CD8+T cells were also promoted at meanwhile. Nevertheless, in vitro, lung cancer cells and MDSC were not directly inhibited by Ze-Qi-Tang and the proliferation of T cells were not directly promoted by it either. Based on these work, we propose a hypothesis that in tumor microenvironment the suppressive effect of Ze-Qi-Tang on lung cancer cells via down-regulating S100A9 to inhibit G-MDSC to enhance the killing ability of CD8+T cells to reshape the tumor microenvironment. To verify the hypothesis, this topic will be around: 1 The overall analysis of tumor suppressive effect of Ze-Qi-Tang ; 2 Whether G-MDSC is the target for Ze-Qi-Tang to inhibit tumor growth; 3 The molecular mechanism of Ze-Qi-Tang via down-regulating S100A9 to inhibit G-MDSC in tumor microenvironment, taking advantage of the technology of molecular biology and molecular immunology to reveal the mechanism of tumor suppressive effect of Ze-Qi-Tang, and providing modern scientific support for the clinical treatment of lung cancer.