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微生物群触发了瘤微环境的STING型I IFN依赖单细胞重编程

Khiem C Lam¹, Romina E Araya¹, April Huang²

¹Inflammatory Cell Dynamics Section, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

|October 8, 2021

概括

微生物群信号编程瘤免疫细胞, 增强抗癌反应. 通过调节肠道瘤轴, 高纤维饮食和便移植提高了治疗效果.

科学领域:

免疫学
癌症学
微生物组研究

背景情况:

瘤微环境 (TME) 极大地影响癌症的进展和治疗结果.
了解TME免疫细胞的调节对于开发有效的癌症疗法至关重要.

研究的目的:

研究微生物群信号如何影响TME的免疫组成.
阐明微生物群调节抗瘤免疫力的机制.
通过微生物群的操纵来提高癌症免疫疗法的策略.

主要方法:

单细胞RNA测序用于在微生物群存在或不存在的情况下分析TME免疫细胞.
涉及干扰素基因刺激剂 (STING) 激动剂和I型干扰素 (IFN-I) 生产的机制研究.
使用高纤维饮食和便微生物群移植 (FMT) 调节微生物群.
在接受免疫检查点阻塞 (ICB) 的黑色素瘤患者中进行验证.

主要成果:

微生物群的缺失使TME偏向于原发瘤的巨细胞.
来自微生物群的STING激动剂诱导单细胞的IFN- I产生,促进免疫刺激细胞和增强NK细胞- DC交叉声.
高纤维饮食和FMT调节了内IFN- I- NK细胞- DC轴,改善了ICB的疗效.
受试者和不受试者之间的内IFN- I水平和免疫组成差异可以通过FMT转移.

结论:

微生物群信号对于TME中的单核细胞向免疫刺激表型编程至关重要.
微生物群-IFN-I-NK细胞-DC轴是将肠道微生物与先天抗瘤免疫联系起来的关键机制.
针对微生物群提供了一个有希望的策略来提高像ICB这样的癌症免疫疗法的有效性.

关键词:

一个癌症免疫学树突细胞免疫检查点阻断免疫疗法天生的免疫力干扰素巨细胞微生物群单细胞瘤微环境

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