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Toll样受体激动剂对人γδT细胞抗肿瘤功能的促进作用及机制研究
结题报告
批准号:
31970843
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
陈慧
学科分类:
肿瘤免疫微环境
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
陈慧
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中文摘要
TLR激动剂作为增强机体抗肿瘤免疫应答的佐剂,被广泛应用于肿瘤的免疫治疗中。作为一种特殊的T细胞,γδT细胞表达多种TLR。其组织趋向性和早期活化、固有免疫样的MHC非限制性方式直接识别广谱的肿瘤相关抗原、强大的细胞毒活性和细胞因子分泌功能以及简便实用的体外扩增体系,让它在更具异质性的实体肿瘤细胞过继免疫治疗中更具优势。.本研究着眼于TLR和γδT细胞,旨在全面系统研究TLR激动剂对人γδT细胞抗肿瘤功能的促进作用及机制,研究将从TLR激动剂对效应性γδT细胞的促进作用和对调节性γδT细胞的抑制作用两方面展开,并深入揭示其可能的机制。研究结果一方面将能直接应用于已有的处于临床试验阶段的基于γδT细胞的肿瘤细胞过继免疫治疗,通过优化γδT细胞的培养条件,大大增强其疗效;另一方面,与疗效相关的可能的药物靶点,将为基于γδT细胞的肿瘤免疫治疗提供新的组合思路。
英文摘要
The role of Toll-like receptor (TLR) agonists in tumor immunotherapy is being confirmed by more and more studies. They are widely used as adjuvants to enhance the anti-tumor immune response by promoting antigen presentation in tumor patients. Gamma Delta T cells play an important role in the process of linking innate and adaptive immune responses. As an innate immune-like T cells, gamma delta T cells express many kinds of TLR. Its tissue orientation and early activation, innate immune-like MHC non-restrictive way directly identifies broad-spectrum tumor-associated antigens, strong cytotoxicity and cytokine secretion function, and simple and practical in vitro amplification system, makes it more advantageous in adoptive immunotherapy of more heterogeneous solid tumor cells..This study will focus on TLR and gamma-delta T cells and aim at the promoting effects of TLR agonists, on human gamma-delta T cells. Both the promotion on effector gamma-delta T cells and inhibition effect on regulatory gamma-delta T cells will be included to reveal possible mechanisms. On one hand, the results will be directly applied to gamma-delta T cells adoptive immunotherapy, which is in the stage of clinical trials, to enhance the therapeutic effect by optimizing the in vitro culture conditions of gamma-delta T cells. On the other hand, potential drug targets related to therapeutic effects will provide a new combination strategy for tumor immunotherapy based on gamma-delta T cells.
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DOI:10.1097/cm9.0000000000002781
发表时间:2024-01-05
期刊:Chinese medical journal
影响因子:6.1
作者:
通讯作者:
DOI:--
发表时间:2020
期刊:基础医学与临床
影响因子:--
作者:王玥;李 峥;陈 慧;张建民;何 维
通讯作者:何 维
Anti-PD-1 antibody armored γδ T cells enhance anti-tumor efficacy in ovarian cancer.
抗PD-1抗体装甲γδT细胞增强了卵巢癌的抗肿瘤功效。
DOI:10.1038/s41392-023-01646-7
发表时间:2023-10-20
期刊:SIGNAL TRANSDUCTION AND TARGETED THERAPY
影响因子:39.3
作者:Wang, Yue;Han, Jingyi;Wang, Dongdong;Cai, Menghua;Xu, Yi;Hu, Yu;Chen, Hui;He, Wei;Zhang, Jianmin
通讯作者:Zhang, Jianmin
DOI:10.37349/ei.2022.00035
发表时间:2022-02
期刊:Exploration of Immunology
影响因子:--
作者:Xiangjin Zhang;Yi Xu;Hui Chen;Jianmin Zhang;Wei He
通讯作者:Xiangjin Zhang;Yi Xu;Hui Chen;Jianmin Zhang;Wei He
DOI:10.37349/ei.2022.00037
发表时间:2022-02
期刊:Exploration of Immunology
影响因子:--
作者:Chang Liu;Yi Xu;Jianmin Zhang;Wei He
通讯作者:Chang Liu;Yi Xu;Jianmin Zhang;Wei He
肿瘤相关TCRγδ CDR3免疫组库研究及基于优势CDR3序列的γδT细胞所识别的肿瘤相关配体筛选
国内基金
海外基金