Th9细胞及其免疫微环境对恶性腹腔积液的影响机制

多种恶性肿瘤患者晚期会发生恶性腹腔积液（MA）。目前国内外尚未见有关于Th9细胞在MA免疫微环境中作用机制的研究报道。本项目将在前期的工作基础上揭示 MA 环境中 Th9 细胞的表型和功能特征及其与临床指标之间的关系；确定MA 中是否存在作为Th9 细胞发生和分化所需要的各种细胞因子，揭示合成和释放上述细胞因子的细胞来源和机制；在体外实验中阐明Th9 细胞发生、分化和增殖所需要的最适宜条件，并阐明Th9 细胞与其他免疫细胞如调节性T 细胞、Th17、Th22细胞等之间的相互作用及其作用机制；阐明肿瘤细胞和腹腔其他细胞对Th9 细胞的分化和扩增的影响；揭示Th9 细胞浸润到腹膜腔的机制及其对 MA 转归的影响。本项目的完成将有助于加深人们对MA 发生机制的认识，找出对MA 具有鉴别诊断价值的免疫学指标，并为治疗晚期恶性肿瘤提出重要的靶标分子，具有重要的科学意义和应用价值。

Several malignant tumors will incur malignant ascites (MA) at the advanced stage.Currently, no previous studies investigated the role of Th9 cells in the MA. This study will extend our previous works and 1) will elucidate the phenotypic and functional characteristics of Th9 cells in MA tumor environment, and their association with various clinical parameters; 2) will identify the presence or absence of various cytokines requiring for generation and differentiation of Th9 cells, the cell origins of these cytokines, as well as the mechanisms by which synthesis and release of cytokines are affected; 3) will explore the optimal conditions for Th9 cell generation, differentiation, and proliferation in vitro experiments, and the interaction and mechanism between and the other immune cells, including regulatory T cells, Th17 cells and Th22 cells; 4) will explore the effects of malignant cells on differentiation and expansion of Th9 cells; 5) will elucidate the mechanism by which Th9 cells are recruited into the abdominal cavity, and the impacts of Th9 cells on prognosis of patients with MA. This study will be able to provide the potential immunologic parameters for differentiating MA from abdominal effusions with the other etiologies, and to identify targeting molecules for treating patients with advance malignancies.