多omics概况显示微环境改造是家尘引发的肺癌进展的关键驱动因素
Shams Al-Azzam1, Isabella Stuewe2, Sunandini Sharma3
1Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
概括
长期暴露于家用灰尘虫 (HDM) 通过抑制免疫反应来加速肺癌的生长. 干白素-17A (IL-17A) 在这种免疫抑制中起着关键作用,促进瘤的进展.
科学领域:
- 肺部医学 肺部医学
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 长期暴露于家用灰尘虫 (HDM) 会导致肺炎和DNA损伤.
- 人体瘤对肺癌发展的影响尚不清楚.
研究的目的:
- 调查慢性HDM暴露对肺癌进展的影响.
- 阐明HDM驱动的瘤促进背后的分子和免疫机制.
主要方法:
- 全基因组测序,RNA测序和DNA甲基化概况被用于肺上皮细胞系和小鼠肺癌模型.
- 使用了免疫解密和遗传淘汰模型 (Il17a-/- 和Il1b-/-).
主要成果:
- 暴露于HDM加速了瘤的生长,而没有增加突变负担.
- 高血压改变了肺部微环境,增强了正常肺组织的炎症,但抑制了免疫反应,T细胞活性和瘤中的抗原呈现.
- 观察到转向髓质丰富和淋巴细胞抑制的转变,细胞毒性T和NK细胞特征减少.
- 通过HDM促进瘤依赖于IN-17A (IL-17A).
结论:
- 长期暴露于空气过敏原,特别是HDM,通过创造一种免疫抑制的微环境,促进肺癌的进展.
- IL-17A是HDM驱动的肺瘤促进的关键调解者.
- 向IL-17A可能在过敏炎症的背景下为肺癌提供治疗策略.
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