可转移的元素通过RIG-I介导的病毒感应通路强化放射治疗诱导的细胞免疫反应
Junyan Du1, Shun-Ichiro Kageyama2,3, Riu Yamashita1,4
1Division of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
Communications biology
|August 5, 2023
概括
放射疗法与免疫疗法相结合显示出有希望的结果,但机制尚不清楚. 这项研究揭示了可移植元素 (TEs) 辐射后激活RIG-I通路,在肺癌和食道癌症中增强抗瘤免疫力.
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:
- 放射疗法 (RT) 加上免疫疗法是一种有前途的癌症治疗方法,但其疗效受到治疗效果不足和对潜在分子机制缺乏理解的限制.
- 澄清这些机制对于开发更有效的组合疗法至关重要.
研究的目的:
- 在放射治疗后,研究推动非小细胞肺癌 (NSCLC) 和食道状细胞癌 (ESCC) 的细胞免疫反应的分子机制.
- 为了确定关键的调节者和RNA病毒传感器通路的配体,参与辐射后的抗瘤免疫力.
主要方法:
- 使用的细胞系 (NSCLC和ESCC) 和患者组织 (ESCC).
- 采用RNA病毒传感器路径分析,包括RIG-I激活.
- 在mTOR-LTR-RIG-I轴上进行了机制研究.
- 进行了单细胞RNA测序 (scRNA) 和空间转录组分析.
主要成果:
- RNA病毒传感器通路,特别是涉及RIG-I,在调节NSCLC和ESCC中的细胞免疫反应方面发挥着主导作用.
- 可转换元素 (TE),特别是长终端重复 (LTR),作为RIG-I的关键连接体.
- 辐射后mTOR-LTR-RIG-I轴被激活,增强细胞免疫反应并促进树突细胞和巨细胞的透.
- 在ESCC患者组织中证实了依赖RIG-I的免疫激活.
- 放射治疗诱导LTR表达并激活免疫和癌细胞中的RNA病毒传感器通路,从而导致"热"的瘤免疫微环境.
结论:
- mTOR-LTR-RIG-I轴是调解癌症中对放射治疗的免疫反应的关键途径.
- 可转移元素 (LTR) 作为RIG-I的关键连接体,桥梁放射治疗和免疫激活.
- 了解这种途径为增强联合放射治疗和免疫治疗的疗效提供了新的目标.
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