为了探讨分泌白介素-9的CD4+ T细胞（Th9细胞）及其免疫微环境对恶性胸腔积液（MPE）的影响及其机制，本项目将在以前工作的基础上揭示MPE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MPE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、巨噬细胞、间皮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MPE转归的影响。本项目的完成将有助于加深人们对MPE发生机制的认识，找出对MPE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。

In order to investigate the impacts and mechanisms of interleukin-9-producing CD4+ T cells (Th9 cells) and their immune micro-environment on malignant pleural effusion (MPE), this study will extend our previous works and 1) will elucidate the phenotypic and functional characteristics of Th9 cells in MPE 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 in vitro experiments, and the interaction and mechanism between Th22 cells and the other immune cells, including regulatory T cells, macrophages, and pleural mesothelial cells; 4) will explore the effects of malignant cells and the other pleural cells on differentiation and expansion of Th9 cells; 5) will elucidate the mechanism by which Th9 cells are recruited into the pleural space, and the impacts of Th9 cells on prognosis of patients with MPE. This study will be able to provide the potential immunologic parameters for differentiating MPE from pleural effusions with the other etiologies, and to identify targeting molecules for treating patients with advance malignancies.