促进抗瘤免疫力并促进抗PD-L1疗效
Ayelet Sivan1, Leticia Corrales1, Nathaniel Hubert2
1Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
概括
肠道微生物群, 特别是Bifidobacterium, 可以增强身体对黑色素瘤的自然防御. 补充Bifidobacterium可以改善瘤控制,类似于检查点阻塞疗法,并且将它们结合起来几乎可以消除瘤生长.
科学领域:
- 免疫学
- 微生物组研究
- 癌症生物学
背景情况:
- 固体瘤中的T细胞透与更好的患者预后相关.
- 不同的抗瘤免疫反应背后的机制尚未完全理解.
- 肠道微生物群是影响个体免疫反应的潜在因素.
研究的目的:
- 研究肠道微生物群在调节自发抗瘤免疫力的作用.
- 确定与增强抗瘤反应相关的特定微生物物种.
- 评估微生物群操纵在癌症免疫治疗中的治疗潜力.
主要方法:
- 在不同肠道微生物组合的小鼠中比较黑色素瘤生长.
- 在共同安置或便微生物移植后对免疫反应的评估.
- 测序16S核糖体RNA基因以识别关键的微生物种类.
- 评估单独使用Bifidobacterium以及与PD- L1阻断药物联合使用.
- 在瘤微环境中分析树突细胞功能和CD8 ((+) T细胞反应.
主要成果:
- 在黑色素瘤模型中,明显的开始微生物群影响了自发的抗瘤免疫力.
- 抗瘤免疫的差异可以通过共同住宿或便转移.
- Bifidobacterium被确定为与抗瘤作用相关的关键微生物成分.
- 单独口服Bifidobacterium可以改善瘤控制,与PD- L1阻塞相比.
- 用Bifidobacterium和PD-L1阻断的联合治疗几乎消除了瘤的增长.
- 在瘤中观察到增强的树突细胞功能和增加的CD8 ((+) T细胞原始化和积累.
结论:
- 肠道微生物组合显著影响宿主产生抗瘤免疫反应的能力.
- 双杆菌在促进抗瘤免疫力方面发挥着至关重要的作用,可能是通过增强T细胞反应.
- 准肠道微生物群是加强癌症免疫疗法的有希望的策略,
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