TNFR2调控Treg及肿瘤细胞参与宫颈癌发生发展的作用及机制研究

免疫逃逸是促进肿瘤进展的重要原因，已证明Treg在肿瘤免疫逃逸中发挥主要作用。TNFR2能调控Treg分化及功能，还能直接调控肿瘤细胞生物学行为参与多种肿瘤的发生发展，但TNFR2在宫颈癌中的作用尚未可知。我们前期发现宫颈癌中存在TNFR2+Treg比例增加且与临床分期相关;还发现宫颈癌组织TNFR2表达显著高于正常宫颈，干扰其表达能抑制肿瘤增殖。结合文献及前期结果我们提出：TNFR2可能通过调控Treg分化及功能、直接调控肿瘤细胞恶性行为双重途径参与宫颈癌的发生发展。本课题拟通过流式细胞技术、磁珠分选、免疫组化、悬浮芯片、动物实验等技术，揭示宫颈癌中TNFR2在Treg和肿瘤细胞中的表达变化及其与临床病理指标的关系，体外实验阐明TNFR2调控Treg细胞及宫颈癌细胞生物学行为参与宫颈癌发生发展的机制并通过动物模型进一步验证。本项目的预期成果将为发现宫颈癌免疫治疗的新靶点提供理论支持。

Immune escape is an important reason to promote tumor progression and Treg has been proved to play a major role in tumor immune escape. Recently, it has been reported that tumor necrosis factor receptor 2 (TNFR2) plays a vital role in the equilibrium and function of both Treg and cancer cells. TNFR2 could accelerate the development of various kinds of cancer by hampering effective anti-cancer immunity and promoting the growth of cancer cells directly. However, the role of TNFR2 in the progression of cervical cancer remains mysterious. Previously, our studies have confirmed that the increase in the proportion of TNFR2+Treg in cervical cancer is related to the clinical stage of cervical cancer. It was found that TNFR2 was mainly expressed by cervical cancer cells and could hardly be detected in normal cervical tissues. Based on previous research, we propose that TNFR2 may assist the development of cervical cancer in two ways, regulating the differentiation and function of Treg to hamper effective anti-cancer immunity, and directly promoting the malignant behaviors of tumor cells. This project intends to determine the expression of TNFR2 in Treg and tumor cells in cervical cancer by flow cytometry, immunohistochemistry, Western blot, suspension chip, and other technologies. We will also explore mechanisms of how TNFR2 regulate the function of Treg and the biological behaviors of cervical cancer cells by in vitro experiment. The findings will be further verified in vivo by animal models. Our research will clarify the role of TNFR2 in the pathogenesis of cervical cancer, and provide new theoretical support for immunotherapy of cervical cancer.