肿瘤微环境内MDSC与卵巢癌干细胞的相互重塑在卵巢癌复发转移中的作用及其分子机制研究

肿瘤免疫逃逸和肿瘤干细胞的存在是肿瘤转移和复发的重要原因。以卵巢癌腹膜转移灶肿瘤微环境内卵巢癌干细胞与MDSC之间的相互作用为切入点，我们联合应用细胞因子抗体芯片技术、miRNA芯片技术及转录组测序 (RNA-Seq) 数据分析发现卵巢癌干细胞与M-MDSC之间存在基于 miR-182-5p与miR-27a相关信号通路的交互调控，且卵巢癌腹膜转移灶内M-MDSC的数量、miR-182-5p与miR-27a的表达与卵巢癌患者的总生存期显著相关。我们设想卵巢癌干细胞与M-MDSC通过相互作用促进卵巢癌腹膜转移灶内免疫抑制微环境的形成，并籍此维持卵巢癌干细胞在免疫压力下的生存、生长和转移。本项目拟从反映实体瘤真实状况的肿瘤免疫抑制微环境出发，探索卵巢癌干细胞与M-MDSC之间相互作用的分子机制及其对肿瘤免疫微环境的调控。研究结果将有助于发现调控卵巢癌免疫抑制微环境的新理论机制。

Immune escape and cancer stem cell play an important role in tumor relapse and metastasis. Based on the interaction between ovarian cancer stem cell and MDSC in tumor microenvironment of ovarian cancer peritoneal carcinomatosis, we find that there is interactive regulation between ovarian cancer stem cells and M-MDSC based on the signal pathways related to microRNA-182-5p and microRNA-27a by using cytokine antibody chip technology, microRNA array, and transcriptome-sequencing (RNA-Seq), and the number of M-MDSC, the expression of microRNA-182-5p and microRNA-27a was significantly correlated with the overall survival of ovarian cancer patients. We hypothesize the interaction between ovarian cancer stem cells and M-MDSC contributes to immunosuppressive microenvironment in peritoneal carcinomatosis of ovarian cancer, thereby promoting the survival, growth and metastasis of ovarian cancer stem cells under immune pressure. This project aims to explore the molecular mechanism of the interaction between ovarian cancer stem cells and M-MDSC and its immune regulation in the tumor microenvironment. The results of this study will contribute to discovering new mechanisms involved in regulating the immunosuppressive microenvironment of ovarian cancer and providing experimental and theoretical basis for exploring novel targets for ovarian cancer treatment.