树突细胞中的YTHDF1损失通过STING依赖的I型IFN生产来增强辐射诱导的抗瘤免疫力
Chuangyu Wen1,2, Liangliang Wang3, András Piffkó1,2,4
1Department of Radiation and Cellular Oncology and.
The Journal of clinical investigation
|September 26, 2024
概括
放射治疗增加了树突细胞中的RNA读者YTHDF1,恶化了癌症的结果. 抑制YTHDF1可以增强放射治疗效果.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- N6-甲基氨酸 (m6A) 阅读器YTHDF1与癌症有关.
- 放射治疗 (RT) 可以影响免疫细胞,包括树突细胞 (DC).
研究的目的:
- 研究YTHDF1在癌症患者和小鼠模型中放射治疗后树突细胞中的作用.
- 探索YTHDF1影响对电离辐射 (IR) 反应的机制.
- 评估针对YTHDF1与RT结合的治疗潜力.
主要方法:
- 从接受RT的癌症患者的外周血液单核细胞 (PBMC) 中分析YTHDF1表达.
- 调查Ythdf1删除在小鼠DC中对IR后抗瘤免疫力的影响.
- 在DC中阐明涉及YTHDF1,STING/IFN-I信号传导和 lysosomal cathepsins的分子途径.
- 在黑色素瘤模型中开发和测试一种针对YTHDF1的DC疫苗,与RT和放射性免疫疗法相结合.
主要成果:
- 在癌症患者的DC中,RT增加了YTHDF1的表达,与糟糕的结果相关.
- 在DC中失去了Ythdf1,在小鼠中增强了DC交叉启动和IR的抗瘤作用.
- 红外线通过STING/IFN-I信号调节了DC YTHDF1;YTHDF1促进了STING降解,减少了IFN-I的产生.
- 一种删除YTHDF1的DC疫苗在小鼠黑色素瘤模型中改善了RT和放射性免疫治疗的疗效.
结论:
- 在DC中,YTHDF1作为对IR反应的STING/IFN-I通路的负调节器.
- 在DC中准YTHDF1是一个有希望的策略,可以提高放射治疗在癌症治疗中的疗效.
- 这项研究揭示了YTHDF1/m6A和STING在对放射治疗的反应中发出信号之间的新型调节轴.
相关概念视频
01:27Cytotoxic T Cells-mediated Immune Response
858
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
858
01:24T Cell Types and Functions
960
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
960
01:22T Cell Activation and Clonal Selection
686
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
686