项目名称： 调节性B细胞在结肠癌中的调节作用及其机制研究

项目编号： No.81502472

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： 刘津麟

作者单位： 杭州医学院

项目金额： 18万元

中文摘要： 结肠癌（CRC）是以机体持续性免疫抑制为特征的一类肿瘤性疾病。调节性B细胞（Breg）是新近发现的一群发挥免疫抑制功能的B细胞亚群。我们前期工作表明：CD19+CD24hiCD27+Breg细胞在CRC病人外周血数量增多且分泌IL-10最多，与肿瘤分期、调节性T细胞（Treg）和髓源性抑制细胞（MDSC）相关，较癌旁组织，Breg细胞在癌组织中也增多，但在CRC中的作用及机制尚不明确。本项目将从CRC病人、动物模型及细胞水平出发，以期明确：1）Breg细胞在CRC病人外周血和癌组织中数量上升、免疫抑制作用增强及介导的免疫调节机制；2）过继转移Breg细胞至CRC荷瘤裸鼠具有促癌作用及其具体机制；3）CRC病人Breg细胞通过抑制CD4+等免疫效应细胞及上调Treg和MDSC等免疫抑制细胞来发挥免疫调节作用或直接促进肿瘤细胞增殖迁移来促进CRC发生发展。从而为CRC的防治提供新的靶点与方向。

中文关键词： 结肠癌；调节性B细胞；免疫抑制

英文摘要： Colorectal cancer (CRC) is a tumor disease characterized by persistant cellular immunology suppression which was caused by dysregulated lymphocyte infiltration in the tumor microenvironment. Regulatory B cells (Breg cell), is a B cell subset which exert immunosuppressive function. Our previous studies reveal that the frequency of CD19+CD24hiCD27+Breg cells, which secrete the highest IL-10, were significantly increased in the PBMC of CRC patients, and associated with the clinical progression, correlated with the regulatory T cell (Treg) and myeloid-derived suppressor cells (MDSC), suggest that the Breg cells play an important role in the pathogenesis of CRC. Compare with the para tumor tissues, the frequency of CD19+CD24hiCD27+Breg cells was also significantly elevated. However, the specific immunoregulatory mechanism of Breg cells and whether play a important role in CRC in vivo is still unclear. In this project, we will identify whether the frequency of Breg cells were increased in a large cohort of CRC patients in peripheral blood mononuclear cells (PBMC) and tumor tissues, Breg cells mediated immunosuppressive function are whether enhanced and specific immunoregulatory mechanism is unknown. Moreover, adoptive transfer method will be used to investigated the function of Breg cells in CRC animal model. Finally, whether the Breg cells can promote the CRC progression through the suppression of the CD4+ effect immune cells or upregulate the Treg and MDSC immunsuppressive cells or direct promote the CRC cell proliferation or migration will be investigated. Understanding the immunoregulatory mechanism of Breg cells in CRC will provide the base for the future immune interventions of the biological cell therapy in CRC patients.

英文关键词： colorectal cancer;regulatory B cell;immune suppression