HMGB1对Treg介导宫颈癌免疫逃逸的影响及机制研究

项目名称： HMGB1对Treg介导宫颈癌免疫逃逸的影响及机制研究

项目编号： No.81202048

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 张瑶

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： 宫颈癌是严重威胁女性健康的一种高发病。目前针对肿瘤细胞免疫逃逸在宫颈癌发病中作用的研究很少。申请者前期研究表明随宫颈病变级别增高及细胞分化程度降低Treg特异性表达因子Foxp3表达水平明显增多，Langer's细胞明显减少，初步证实Treg与宫颈局部免疫调节相关。同时发现随宫颈病变进展HMGB1表达水平明显增加，提示在HPV感染进展为宫颈癌这一过程中HMGB1发挥重要作用。HMGB1抑制剂及RAGE受体封闭剂能够明显抑制宫颈癌荷瘤鼠模型肿瘤生长。结合国际研究进展及前期工作基础，推测HMGB1与RAGE结合，通过调控p38MAPK信号通路，影响Treg介导的免疫逃逸反应，促进宫颈细胞逃避免疫系统"杀伤"，推动"HPV感染-CIN-宫颈癌"这一进程发展，最终导致宫颈癌发生。本项目拟从一个新的视觉出发，全面了解HMGB1对Treg介导宫颈癌免疫逃逸的影响及作用机制，为宫颈癌免疫防治提供新策略。

中文关键词： 宫颈癌；HMGB1；NF-KB；预后；

英文摘要： Persistent infection with HPV caused cervical cancer is a serious threat to women's health. At present，the research about the role of the immune escape of tumor cells in cervical cancer is rare. Our researchs show that Foxp3 expression significantly increased accompanied with the higher levels of cervical lesions and the lower degree of cell differentiation and Langer's cells were significantly reduced. That initially confirmed that Treg was related to the local cervical immune. We also found that the higher levels of cervical lesions the more expression of HMGB1 protein, which suggest HMGB1 play an important role in this process that chronic inflammation caused by HPV infections progress to cervical cancer. EP and anti-RAGE can inhibit tumor growth in tumor-bearing mouse model. Combined with the latest international research foundation and previous study, we guess that HMGB1 with RAGE ligand binding, through the regulation of p38MAPK signaling pathway, affect the escape Treg-mediated immune response, promot cervical cells evade the immune system "kill" to promote the process development of HPV infection to cervical intraepithelial neoplasia to cervical cancer, and ultimately lead to cervical cancer. The project intends to proceed from a new vision, a comprehensive understanding of HMGB1 on the effect and mechan

英文关键词： cervical cancer；HMGB1；NF-KB；prognosis；