用电离辐射治疗的NRF2缺乏的癌细胞促进免疫细胞中的I型干扰素信号传递
Hye-Ran Seo1, Hyo Jeong Kim1, Hwani Ryu1
1Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
Anticancer research
|May 31, 2024
概括
低调核因子与红色素衍生的2相关因子-2 (NRF2) 增强了抗瘤免疫力. 这种策略与电离辐射相结合,通过激活免疫细胞信号通路,将免疫冷瘤转化为热瘤.
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:
- 核因子红色素衍生的2相关因子-2 (NRF2) 是一种转录因子,抑制免疫反应并促进免疫冷瘤微环境.
- 在各种癌症中观察到NRF2的过度表达,包括非小细胞肺癌,有助于瘤进展和免疫逃避.
研究的目的:
- 研究NRF2在调节抗瘤免疫力的作用.
- 通过调节NRF2表达,探索将免疫冷瘤转化为热瘤的策略.
主要方法:
- 在人类和小鼠的癌症细胞系中,NRF2表达被操纵 (敲击或过度表达).
- 细胞被电离辐射或多C处理以刺激免疫反应.
- 评估I型干扰素 (IFN) 水平,细胞质DNA和免疫细胞激活,使用定量实时聚合酶连锁反应,西部抹杀和共同培养试验.
主要成果:
- 下调NRF2增加了I型IFN水平,并激活了cGAS-STING通路,表明免疫信号增强.
- 电离辐射进一步诱导NRF2下调的瘤细胞中的I型IFN.
- 免疫细胞与NRF2降低调节的照射瘤细胞共同培养导致IFNB1和CXCL10的产生增加.
结论:
- 降低NRF2的调节逆转了免疫抑制性瘤微环境,使瘤更容易对免疫治疗做出反应.
- 将NRF2调节与电离辐射相结合,可以有效地将免疫冷瘤转化为热瘤,促进抗瘤免疫反应.
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