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使用先进的微生物组疗法调节瘤免疫力,产生一种内醇代谢产物
Troels Holger Vaaben1, Ditte Olsen Lützhøft1, Andreas Koulouktsis1
1Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, DK2800, Denmark.
EMBO reports
|March 7, 2025
概括
提供英多尔-3-酸的工程细菌通过激活基碳水化合物受体 (AhR) 来增强抗瘤免疫力. 这种基于微生物组的疗法抑制瘤生长并改善存活率,为癌症治疗提供了一种有前途的方法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 肠道微生物组影响免疫反应对抗癌症.
- 微生物的醇代谢产物激活了酸受体 (AhR),影响了免疫细胞的调节.
- 升高的代谢物水平与癌症患者的生存率改善相关.
研究的目的:
- 为了工程细菌增强抗瘤免疫力.
- 研究微生物代谢物在调节瘤微环境中的作用.
- 在癌症模型中评估工程细菌的治疗潜力.
主要方法:
- 设计了埃舍里希亚大肠杆菌尼斯尔1917年,以产生英多尔-3-酸 (一种AhR激动剂).
- 将工程细菌注射到小鼠瘤模型中.
- 分析了瘤微环境的变化,包括细胞因子水平 (CXCL9,IFN-γ) 和T细胞群.
- 通过重新挑战实验评估瘤生长,存活率和长期免疫力.
主要成果:
- 改造后的细菌提供了英多尔-3-酸,改变了瘤的微环境.
- 观察到CXCL9,IFN-γ和瘤透T细胞的丰度和激活的显著增加.
- 治疗抑制了瘤生长,改善了合成基因模型中的存活率,并诱导了长期的抗瘤免疫力.
- 通过英多尔-3-酸直接激活AhR被确定为免疫调节的驱动因素.
结论:
- 基于微生物组的干预措施对癌症治疗具有前途.
- 产生AhR激动剂的工程细菌可以增强抗瘤免疫反应.
- 这种方法调节瘤微环境,导致瘤生长抑制和改善生存率.
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