肠上皮层介素-17受体A信号传递可以通过微生物调节来调节远程瘤的生长
Vidhi Chandra1, Le Li1, Olivereen Le Roux1
1Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer cell
|December 29, 2023
概括
肠道微生物和IL-17信号影响远程瘤生长. 阻断IL-17RA的微生物调节可以克服胰腺癌和脑癌的治疗阻力.
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:
- 介素-17 (IL-17) 信号调节肠道免疫和微生物,但也可以促进瘤生长.
- 肠道IL-17-IL-17受体A (IL-17RA) 信号传递和微生物对远程瘤的影响的作用尚不清楚.
研究的目的:
- 调查由IL-17RA删除驱动的肠道失调如何影响胰腺和脑瘤的生长.
- 阐明微生物依赖IL-17信号传递影响瘤进展和治疗反应的机制.
主要方法:
- 在小鼠模型中,对IL-17RA的系统或肠道上皮质删除.
- 诱导肠道失生症和评估胰腺和脑瘤中的瘤生长.
- 在瘤微环境中分析Th17细胞,B细胞和DUOX2信号.
- 针对性微生物除与IL-17RA抑制相结合的评估.
主要成果:
- 在肠道中删除IL-17RA导致肠道失调,并加速胰腺和脑瘤的生长.
- 观察到Th17细胞和B细胞的增加,这些细胞迁移到遥远的瘤.
- 微生物依赖的IL-17信号增强了瘤细胞内的DUOX2信号.
- 向的微生物剥离使瘤对IL-17RA抑制产生敏感性,克服治疗耐药性.
结论:
- 肠道微生物对IL-17-IL-17RA信号的调节显著影响远程瘤生长和进展.
- 了解肠道微生物群,IL-17信号传递和瘤行为之间的复杂相互作用对于有效的癌症治疗至关重要.
- 向微生物通路提供了一种克服对IL-17RA向疗法的耐药性的策略.
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