CD5(high)的cDC2在肝癌免疫抑制中的作用及其机制研究

批准号:
31700772
项目类别:
青年科学基金项目
资助金额:
25.0 万元
负责人:
尹相云
依托单位:
学科分类:
C0805.肿瘤免疫微环境
结题年份:
2020
批准年份:
2017
项目状态:
已结题
项目参与者:
许勇、金骁扬、聂晓华、王静淑、张柯迪、周志鹏
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中文摘要
人经典树突状细胞(cDC)分为两类:CD141+ 的cDC1和CD1c+ 的cDC2。我们发现,根据CD5表达水平可以将人cDC2分为两个亚群。CD5high DC活化初始CD4+ T细胞的能力较强,并且倾向于诱导其向Treg、Th2或Th22分化;而CD5low DC倾向于诱导Th1分化(J Immunol, 2017)。我们还发现CD5high DC在肝癌组织中富集(未发表数据)。基于以上结果,我们提出如下假说:在肝癌中,CD5high DC通过影响T细胞的分化从而抑制抗肿瘤免疫反应。在本项目中,我们将进行如下研究:1)比较肝癌组织中两群DC诱导CD4+ T细胞分化的能力和方向;2)分析CD5high DC的比例与瘤内T细胞亚群的相关性;3)分析CD5high DC的比例与临床指标的关系。本研究将有利于加深我们对肝癌免疫抑制机制的了解,为肝癌的免疫治疗提供理论依据。
英文摘要
There are two conventional major dendritic cell (cDC) subsets in humans, CD141+ cDC1 and CD1c+ cDC2. Our study showed that human blood cDC2 can be further separated into two subpopulations according to their CD5 expression status. CD5high DC induced naive CD4+ T cell proliferation more potently than did the CD5low DC. Moreover, CD5high DC induced higher levels of Treg, Th2 or Th22 differentiation, whereas CD5low DC induced higher levels of Th1 differentiation (J Immunol, 2017). Our further study showed that the ratio of CD5high DC in hepatocellular carcinoma (HCC) was much higher compared with peripheral blood (unpublished data). Based on the above results, we hypothesize that higher ratio of CD5high DC in HCC could inhibit the antitumor immune response by regulating T cell differentiation. In this project, we propose to further investigate the following several aspects: Firstly, to compare the ability of CD5high and CD5low DC from HCC tissue in inducing CD4+ T cell differentiation. Secondly, to detect the correlation of CD5high DC ratio with T cell type in tumor tissue. Thirdly, to analyze the correlation of CD5high DC ratio with clinical indexes of HCC. This study will advance our understanding in mechanism of immunosuppression of HCC and provide theoretical basis for the development of HCC immunotherapies.
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