关键lncRNAs:难治性EBV-LPD-NK细胞免疫逃逸的潜在机制?

批准号:
81974005
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
郑邈
依托单位:
学科分类:
淋巴瘤与淋巴细胞疾病
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
郑邈
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中文摘要
EB病毒感染NK细胞导致的难治性EBV相关淋巴增殖性疾病(EBV-LPD-NK)国内高发,易并发噬血细胞综合征,生存期短,预后极差。病毒感染能诱导机体表达特异性lncRNAs,广泛调控转录过程,参与免疫逃逸。申请者前期研究显示:与健康人和EB病毒感染B、T细胞所致的淋巴增殖性疾病患者的NK细胞相比,EBV-LPD-NK患者NK细胞有显著差异的“lncRNA表达谱指纹”。据此,提出假说:关键lncRNAs是难治性EBV-LPD-NK免疫逃逸的潜在机制。本项目拟通过比较EBV-LPD患者的T、B、NK细胞的转录组学,明确EBV-LPD-NK的关键lncRNA簇。在体外细胞系中诱导其沉默或过表达,确定与NK细胞免疫监视相关的靶点/通路。建立荷瘤小鼠模型,研究靶向关键lncRNAs或联合其他免疫检查点抑制剂来阻断EBV-LPD-NK的免疫逃逸。这将为难治性EBV-LPD-NK提供一种全新治疗策略。
英文摘要
Refractory EBV-associated lymphoproliferative disease (EBV-LPD-NK) caused by EBV infection with NK cells is highly prevalent in China, which is prone to hemophagocytic syndrome with short survival and poor prognosis. Viral infection can induce the body to express specific lncRNAs, widely regulate the transcription process and participate in immune escape. Our previous studies showed that the expression profiles of lncRNAs in NK cells of EBV-LPD-NK patients were significantly different from those of healthy people and patients with lymphoproliferative diseases caused by B and T cells infected by EBV. Therefore, we hypothesize that the key lncRNAs may be potential mechanisms for immune escape of refractory EBV-LPD-NK. This project aims to validate the key lncRNAs of EBV-LPD-NK by comparing the transcriptome of T, B and NK cells of EBV-LPD. By inducing their silencing or overexpression of NK cells in vitro, targets/pathways related to NK cell immunological surveillance will be identified. EBV-LPD-NK tumor bearing mice model will be established to study targeting key lncRNAs and in combination with other immune checkpoint inhibitors to block EBV-LPD-NK immune escape. This project will provide a new therapeutic strategy for refractory EBV-LPD-NK.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:--
发表时间:2022
期刊:内科急危重症杂志
影响因子:--
作者:包毓函;杨理;杨漾;徐皓;陈丽婷;汪智琼;刘娴;王滢;郑邈
通讯作者:郑邈
DOI:10.1002/hon.2998
发表时间:2022-04
期刊:Hematological Oncology
影响因子:3.3
作者:M. Zheng;Yuhan Bao;Jiachen Wang;Yaxian Ma;Yang Yang-Yang;Peiling Zhang;Liting Chen;Kai Zheng;Jianfeng Zhou
通讯作者:M. Zheng;Yuhan Bao;Jiachen Wang;Yaxian Ma;Yang Yang-Yang;Peiling Zhang;Liting Chen;Kai Zheng;Jianfeng Zhou
DOI:10.1186/s12879-023-08430-6
发表时间:2023-07-07
期刊:BMC INFECTIOUS DISEASES
影响因子:3.7
作者:Ma, Yaxian;Bao, Yuhan;Zheng, Miao
通讯作者:Zheng, Miao
DOI:10.3389/fimmu.2023.1093719
发表时间:2023
期刊:FRONTIERS IN IMMUNOLOGY
影响因子:7.3
作者:Ma, Yaxian;Zhang, Peiling;Bao, Yuhan;Luo, Hui;Wang, Jiachen;Huang, Liang;Zheng, Miao
通讯作者:Zheng, Miao
DOI:10.3389/fimmu.2021.751754
发表时间:2021
期刊:Frontiers in immunology
影响因子:7.3
作者:Ma Y;Yang L;Bao Y;Yang Y;Chen L;Zheng M
通讯作者:Zheng M
血液血管干细胞双向分化促进放射损伤造血重建的机制研究
- 批准号:81300387
- 项目类别:青年科学基金项目
- 资助金额:23.0万元
- 批准年份:2013
- 负责人:郑邈
- 依托单位:
国内基金
海外基金
