肠道微生物组用于预测免疫检查点封锁相关的不良事件
Muni Hu1, Xiaolin Lin2, Tiantian Sun1
1State Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai, 200001, China.
Genome medicine
|January 19, 2024
概括
这项研究确定了从免疫检查点抑制剂 (ICI) 预测免疫相关不良事件 (irAEs) 的肠道微生物. 发现微生物代谢物menaquinone在没有irrAEs的患者中含量较高,这表明其具有治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物组研究 微生物组研究
- 代谢学 代谢学 代谢学
背景情况:
- 免疫检查点抑制剂 (ICI) 可以引起与免疫相关的不良事件 (irAEs).
- 肠道微生物组在irAEs中的作用是已知的,但相关性在不同研究中各不相同.
- 预测IREs仍然是一个挑战.
研究的目的:
- 开发一种基于微生物组的分类器,用于预测irAEs.
- 为了确定与irAEs相关的微生物和代谢因素.
- 探索基础的机制,以发展irAE.
主要方法:
- 发表和内部微生物组数据的全面分析 (16S rRNA和中枪元基因组学).
- 机器学习 (随机森林) 模型构建用于irAE预测.
- 整合转录基因组和元基因组分析,以获得机械学见解.
主要成果:
- 确定了区分irAE和非irAE患者的特定微生物物种.
- 开发了一个具有高区分能力的随机森林分类器 (AUC=0.88).
- 在非irAE患者中发现了增加的menaquinone生物合成和更高的血清menaquinone水平.
结论:
- 微生物生物标志物显示出预测irAE发病的潜力.
- 微生物组衍生代谢物menaquinone可能是调节irAEs的治疗标.
- 这项研究提供了关于ICI治疗中微生物组与宿主相互作用的见解.
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