【2017年整理】恶性肿瘤背景整理.docVIP

摘要：多种恶性肿瘤患者晚期会发生恶性腹水，目前有关Th9细胞在恶性腹水免疫微环境中作用机制鲜有报道。本项目将在前期的工作基础上揭示 恶性腹水 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；确定恶性腹水 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；阐明肿瘤细胞和胸腔其他细胞对Th9 细胞的分化和扩增的影响；揭示Th9 细胞浸润到胸膜腔的机制及其对 恶性腹水 转归的影响。本项目的完成将有助于加深人们对恶性腹水 发生机制的认识，找出对恶性腹水 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 space, 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. 研究背景和意义 多种恶性肿瘤，如肝癌、卵巢癌、胃癌等发展至晚期时，肿瘤细胞侵袭和转移到腹腔可导致恶性胸腔积液，即恶性腹水。发生恶性腹水的患者预后较差，平均生存期约20周。恶性腹水中除了含有肿瘤细胞外，还有大量的免疫细胞如淋巴细胞（主要是CD4+淋巴细胞）、巨噬细胞、粒细胞等。以CD4+为代表T细胞亚群能抑制T细胞对外源和自体抗原的反应，在维持对自身成分免疫耐受的同时也可能阻止机体对自体同源肿瘤的免疫。这些细胞通过分泌多种可溶性炎症和免疫因子，参与肿瘤的生长、转移、扩散等过程。与肝硬化腹水相比，恶性腹水中的CD3+、CD4+、C