项目名称: HIF-1α和STAT3介导乏氧诱导的PD-L1上调在鼻咽癌免疫逃逸中的作用及机制研究
项目编号: No.81502355
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 黄岩
作者单位: 中山大学
项目金额: 16万元
中文摘要: 鼻咽癌是一个血管网丰富但乏氧明显的肿瘤,其癌巢中有大量的淋巴细胞浸润却难以发挥抗肿瘤免疫作用。既往研究表明乏氧可能是介导免疫抑制微环境形成的一个重要机制,我们在预实验中则首次发现鼻咽癌细胞中,乏氧可诱导程序性死亡配体1(PD-L1)的上调,并且PD-L1与乏氧诱导因子1α(HIF-1α)表达水平以及JAK2/STAT3通路的活化密切相关。我们还发现索拉非尼治疗后进展的鼻咽癌组织中,HIF-1α和PD-L1明显上调。因此我们假设,乏氧可能通过诱导HIF-1α及活化STAT3,从转录水平上调PD-L1,从而介导鼻咽癌免疫逃逸的发生。本课题将分别研究HIF-1α及STAT3介导乏氧下PD-L1上调的分子机制及其在鼻咽癌免疫逃逸中的作用。本研究将加深我们对鼻咽癌免疫逃逸机制的理解、揭示乏氧在鼻咽癌治疗耐药中的新机制,为肿瘤防治提供理论依据及新的靶点。
中文关键词: 鼻咽癌;乏氧;乏氧诱导因子-1α;JAK2/STAT3;程序性死亡配体-1
英文摘要: Nasopharyngeal carcinoma (NPC) is characterized by abundant vasculature but is also significantly presented with hypoxia. NPC nests are usually infiltrated by lymphocytes which are incapable of eliminating those cancer cells. Several studies have revealed that hypoxia might be an important mechanism leading to the formation of immune suppression microenvironment. Our preliminary study for the first time shows that hypoxia could induce the expression of Programed Death-ligand 1 (PD-L1), which is closely related to the level of Hypoxia-inducible Factor-1α (HIF-1α) and the activation of JAK2/STAT3. We therefore hypothesize that hypoxia could mediate the immune evasion of NPC via the up-regulation of PD-L1, which might be transcriptionally regulated by HIF-1α and STAT3. This project could deepen our understanding of immune evasion in NPC; reveal the new mechanism of drug-resistance mediated by hypoxia in NPC; and provide new theory and target for cancer prevention and treatment.
英文关键词: Nasopharyngeal Carcinoma;Hypoxia;Hypoxia-inducible Factor-1α;JAK2/STAT3;Programmed Death-ligand 1