乙型肝炎病毒通过调节对环境致癌物质的免疫反应来促进肝癌
Mei Huang1,2,3, Dongyao Wang1,2,4, Jiao Huang1,2
1Center for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nature communications
|June 27, 2025
概括
乙型肝炎病毒 (HBV) 不仅仅会导致肝癌. 环境致癌物,如DEN,结合HBV激活IL-33信号,促进肝炎和癌症. 皮塔瓦斯塔丁抑制了这种途径,降低了HBV携带者的癌症风险.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
背景情况:
- 乙型肝炎病毒 (HBV) 感染与肝炎和肝细胞癌 (HCC) 有关.
- 连接HBV与肝病和癌症的确切机制,特别是在无症状个体中,仍然不清楚.
- 了解这种联系对于制定有效的预防和治疗策略至关重要.
研究的目的:
- 阐明HBV导致肝癌的机制.
- 研究环境因素和特定分子途径在HBV相关肝癌中的作用.
- 评估IL-33抑制在预防HBV相关HCC的治疗潜力.
主要方法:
- 在小鼠肝脏中长期表达HBV基因组.
- 给小鼠使用致癌物二甲基尼托拉胺 (DEN).
- 对介质蛋白-33 (IL-33) /调控性T细胞轴的分析.
- 用皮塔瓦斯塔丁治疗,它是一种IL-33抑制剂.
- 对HBV阳性肝炎患者的临床数据分析.
主要成果:
- 单独的HBV并没有诱导小鼠的肝炎或癌症.
- 对HBV基因组表达和DEN的联合暴露显著增加了肝炎和癌症倾向.
- IL-33 /调节性T细胞轴对于HBV以及DEN诱导的肝癌发生是必不可少的.
- 在小鼠中,皮塔瓦斯塔丁治疗抑制了HBV以及DEN诱导的肝癌.
- 在HBV阳性肝炎患者中观察到IL-33水平升高,而皮塔瓦斯塔丁的使用与肝炎和HCC风险降低相关.
结论:
- 环境致癌物,而不仅仅是HBV,是HBV携带者中HCC风险增加的关键联系.
- IL-33/调节性T细胞通路在HBV感染的背景下,在由致癌物引起的肝癌发生中起着关键作用.
- 用像皮塔瓦斯塔丁这样的抑制剂向IL-33提供了一种潜在的策略,用于预防HBV感染个体的肝癌.
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