功能失调的昼夜时钟加速了肠道微生物群的癌症转移,引发了骨髓衍生抑制细胞的积累
Jing-Lin Liu1, Xu Xu2, Youlutuziayi Rixiati2
1Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Cell metabolism
|June 5, 2024
概括
昼夜节律和肠道细菌代谢物taurocholic 酸的干扰通过影响骨髓衍生抑制细胞 (MDSCs) 来促进结直肠癌 (CRC) 转移. 这项研究揭示了连接生物钟,肠道微生物群和癌症传播的系统机制.
科学领域:
- 在瘤学瘤学.
- 时间生物学 时间生物学
- 免疫学 免疫学 免疫学
背景情况:
- 循环静止对于哺乳动物对环境线索的反应至关重要.
- 昼夜节律,瘤微环境 (TME) 和癌症转移之间的关系在很大程度上仍未被探索.
- 结肠直肠癌 (CRC) 转移是一个重大的临床挑战.
研究的目的:
- 研究昼夜节律扰乱与结直肠癌 (CRC) 转移中的TME之间的相互作用.
- 阐明肠道微生物群及其代谢物在促进CRC肺转移中的作用.
- 揭示生物节律失调和肠道代谢物影响癌细胞传播的分子机制.
主要方法:
- 在CRC患者中分析昼夜节律和免疫细胞群.
- 用小鼠模型研究昼夜调节失调对CRC肺转移的影响.
- 研究肠道微生物群和陶罗胆酸 (TCA) 在促进转移中的作用.
- 在骨髓系衍生抑制细胞 (MDSCs) 中对表观遗传修饰和蛋白质无化进行分子分析.
主要成果:
- 昼夜节律的干扰和单细胞/粒细胞的增加与CRC转移相关.
- 循环节失调通过增加肺MDSC和损害小鼠CD8+T细胞来促进肺转移.
- 肠道微生物群和TCA通过触发MDSC积累,导致肺转移.
- TCA在表观遗传上增强了MDSC糖解,并抑制了PDL1的无处不在.
结论:
- 循环节律障碍和肠道微生物群代谢物,特别是TCA,是结直肠癌 (CRC) 转移的关键驱动因素.
- 这项研究确定了生物钟,MDSCs和肠道微生物群之间在控制CRC转移传播方面的新联系.
- 这项研究揭示了在癌症转移中涉及肠-TME-循环轴的系统机制,提供了潜在的治疗点.
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