本课题主要研究肿瘤相关巨噬细胞(TAM)在卵巢癌肿瘤异质性中的作用及相关调控机制。首先，采用免疫组化方法和流式细胞学方法，在组织芯片和新鲜组织标本中进检测TAM在不同部位的表型。将来自同一卵巢癌细胞母系的侵袭能力不同的单克隆亚系与人原代巨噬细胞共培养，采用流式细胞学方法，检测不同侵袭能力的卵巢癌细胞上清对TAM表型的诱导作用，证明卵巢癌微环境中TAM存在表型异质性。其次，为了明确TAM在卵巢癌发生发展过程中的作用，我们将卵巢癌细胞与人原代巨噬细胞共培养，诱导TAM表型改变，用所收集的上清液处理卵巢癌细胞，比较处理前后卵巢癌细胞生物学功能的改变。再次，为了了解TAM在卵巢癌肿瘤异质性中的作用机制，我们收集卵巢癌细胞的培养上清液，将上清液与人原代巨噬细胞共培养，诱导TAM表型改变，利用细胞因子抗体芯片和miRNA芯片，筛选处理前后表达具有差异性的蛋白分子和miRNA分子，并进行生物信息学分析。

Our research mainly focuses on the functions and mechanisms of tumor associated macrophage (TAM) in tumor heterogeneity in ovarian cancer. First, we use immunohistochemical and flow cytometric methods to detect the phenotype of TAM in different specimen from the same patients with advanced ovarian cancer. Additionally, flow cytometric method will be adopted to detect the phenotype change of macrophages after co-culture with highly aggressive and less aggressive subclonings of ovarian cancer cells, to prove the existence of phenotype heterogeneity of TAM in the microenvironment of ovarian cancer. Second, to explore the functions of TAM in ovarian cancer development, we will compare the changes in biological behaviors of ovarian cancer cells after co-culture with supernatant of TAM, mainly through in vivo and in vitro experiment. Third, we will detect the changes in cytokines and miRNAs of TAM after co-culture with supernatant of ovarian cancer cells, to explore the possible mechanisms of TAM in tumor heterogeneity in ovarian cancer to provide potential targets for treatment.