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肠道微生物群落和代谢物之间的相互作用调节了全癌症免疫疗法反应

Xiaoqiang Zhu¹, Muni Hu², Xiaowen Huang²

¹State Key Laboratory of Systems Medicine for Cancer, Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, Renji Hospital, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Gastroenterology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Cell metabolism

|February 5, 2025

概括

肠道微生物组及其代谢物影响癌症免疫治疗的有效性. 研究人员确定了特定的微生物和代谢特征,包括甲胺 (PAGln),可以预测对免疫检查点阻塞疗法的反应.

科学领域:

在瘤学瘤学.
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:

免疫检查点阻塞 (ICB) 疗法,针对编程细胞死亡蛋白1 (PD-1) /编程死亡连接体1 (PD-L1),已经改变了癌症治疗.
然而,ICB的疗效仅限于一小部分患者,因此需要确定预测性生物标志物.
肠道微生物组及其代谢物越来越被认为是ICB反应的关键调节剂.

研究的目的:

研究肠道微生物和代谢特征与对抗PD-1/PD-L1治疗的反应之间的关联.
为了确定可预测ICB治疗结果的微生物和代谢特征.
探索特定代谢物的功能作用,如甲胺 (PAGln),在调节ICB疗效.

主要方法:

来自接受抗PD-1/PD-L1治疗的165名患者的便样本的多组组学分析 (元基因组学和代谢学).
在四个公共元基因组数据集 (n=568) 和一个独立队列 (n=138) 中整合和验证微生物和代谢特征.
一个综合预测模型的开发和响应相关的肠类型的表征.

主要成果:

识别与ICB治疗反应相关的跨队列微生物和代谢特征.
开发一个强大的预测模型,结合这些特征.
发现了与特定细菌种群和代谢物相关的五种不同的响应相关肠型.
在体内发现,乙谷氨 (PAGln) 与反应和减弱的抗PD-1疗效有负相关性.

结论:

肠道微生物组和代谢组在调节免疫检查点阻塞疗法的有效性方面发挥着重要作用.
特定的微生物和代谢特征,包括PAGln,可以作为预测ICB反应的潜在生物标志物.
了解这些宿主-微生物-代谢物相互作用为改善免疫治疗结果提供了机会.

关键词:

进入类型进入类型进入类型便微生物群移植我们的肠道微生物组.免疫疗法免疫疗法代谢生物组的代谢生物组甲基氨酸氨基胺是什么

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