协同刺激分子B7-H3在结直肠癌发生、发展过程中的作用和机制

项目名称： 协同刺激分子B7-H3在结直肠癌发生、发展过程中的作用和机制

项目编号： No.81201600

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1

项目作者： 茆勇

作者单位： 苏州大学

项目金额： 23万元

中文摘要： 结直肠癌的发生呈现从息肉、腺瘤、高级别瘤变等病变缓慢发展至癌的漫长过程，与肿瘤免疫逃逸机制密切相关。而协同刺激分子B7-H3是肿瘤微环境中参与免疫逃逸的重要分子。我们的研究发现：在B7家族（B7-H1、B7-H3、B7-H4）中，B7-H3在息肉、腺瘤阶段表达即上调，并随着病变发展逐步增高，与肿瘤浸润T淋巴细胞及巨噬细胞数量、功能密切相关，提示B7-H3信号是结直肠癌发生的早期事件，可能是肿瘤早期诊断和逆转治疗的靶分子，对肿瘤的细胞免疫存在复杂的调控机制。鉴此，本项目在研究 B7-H3分子动态表达的基础上，利用Apc(Min/+)小鼠结直肠癌模型，模拟结直肠癌发生的三个免疫时相，诱导结直肠癌发生，然后早期阻断B7-H3信号，观察其对APC(Min/+)小鼠模型肿瘤发生的影响，探讨阻断B7-H3信号在结直肠癌的预防和治疗中的作用机制，为结直肠癌的早期诊断及靶向治疗提供新的干预策略。

中文关键词： 结直肠癌；B7-H1；B7-H3；B7-H4；肿瘤免疫

英文摘要： Showing the occurrence of the lengthy process from polyp, adenoma, high-level neoplasia lesions to colorectal cancer, and tumor immune escape mechanism closely related. Costimulatory molecules B7-H3 is an important molecule involved in immune escape in the tumor microenvironment. Our study shows that: the B7 family (B7-H1, B7-H3, B7-H4), B7-H3 is the first expression molecular in the occurrence of colorectal cancer，in the polyp, adenoma stage expression increasing, and closely related of the number and functions of tumor-infiltrating T lymphocytes and macrophages, suggesting that B7-H3 signal is an early event in colorectal carcinogenesis, may be the target molecules of the tumor early diagnosis and reversal of treatment. In this context, the project on the basis of analysis of the expression of B7-H3 molecular dynamics, build Apc (Min / +) mouse colorectal cancer model, simulate cancer three immune phase，early blocking B7-H3 signal, observe the APC (min / +) mouse model of tumorigenesis to explore the mechanism of blocking B7-H3 signal in the prevention and treatment of colorectal cancer, early diagnosis and targeted therapy for colorectal cancer provide new intervention strategies.

英文关键词： colorectal cancer；B7-H1；B7-H3；B7-H4；tumor immunity