与结直肠癌相关的关键病原生物促进了瘤性重编程
Josh Jones1, Qiaojuan Shi1, Rahul R Nath1
1Meinig School for Biomedical Engineering, Cornell University, Ithaca, NY, United States of America.
PloS one
|February 16, 2024
概括
两种肠道细菌,Fusobacterium nucleatum (Fn) 和内毒性细菌 Bacteroides fragilis (ETBF),通过促进癌症干细胞样肠细胞和损害T细胞功能,恶化结肠直肠癌 (CRC).
科学领域:
- 微生物学 微生物学
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
背景情况:
- 杆菌核酸菌 (Fn) 和肠毒性细菌 (ETBF) 是与结直肠癌 (CRC) 相关的肠道病原生物.
- 它们对CRC肠道表皮和免疫微环境的具体影响尚不清楚.
研究的目的:
- 研究Fn和ETBF对肠表皮和免疫细胞在CRC小鼠模型中的影响.
- 为了阐明病原体驱动的CRC恶化背后的分子机制.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 在野生型小鼠和暴露于Fn和ETBF的CRC小鼠模型上进行.
- 分析了表皮和免疫细胞的转录变化.
主要成果:
- 在CRC小鼠模型中,Fn和ETBF在肠细胞中强化了类似癌症的转录表现型.
- 虽然对病原生物的暴露增加了野生型小鼠的T细胞,但在CRC模型中,这种效应失去了.
- 观察到Myc信号和脂肪酸代谢的病原体特异性变化.
结论:
- 通过诱导癌症干细胞样肠细胞,Fn和ETBF促进CRC瘤发生.
- 这些病原生物破坏细胞毒性T淋巴细胞 (CTL) 功能,导致CRC进展.
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