减少 metionin 的工程益生菌通过激活 STING 途径来促进 PD-L1 抗体免疫治疗
Tiantian Sun1, Qiushuang Zhang2, Yicong Dai3
1Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, 266071, China.
Biomaterials
|January 28, 2026
概括
工程益生菌 (Met-EcN) 向瘤氨酸,增强免疫疗法. 这种方法增强了抗PD-L1的疗效,在临床前模型中增加了瘤抑制和生存率.
科学领域:
- 在瘤学瘤学.
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
背景情况:
- 与正常组织相比,瘤细胞表现出较高的氨酸依赖性.
- 目前的氨酸限制方法在临床应用中面临挑战,原因是毒性和向性差.
- 向瘤特定的代谢脆弱性提供了一个有前途的治疗途径.
研究的目的:
- 开发一种工程化益生菌 (Met-EcN),用于瘤微环境中的氨酸食量.
- 在临床前癌症模型中评估Met-EcN与抗PD-L1免疫疗法结合的疗效.
- 阐明Met-EcN介导的免疫激活的潜在机制.
主要方法:
- 开发一种基因工程益生菌 (Met-EcN) 用于有针对性的甲素耗尽.
- 在体内研究使用B16-F10黑色素瘤和MC-38结肠癌小鼠模型.
- 评估瘤生长抑制,存活率,T细胞透和激活以及免疫信号通路 (cGAS-STING).
主要成果:
- 在黑色素瘤和结肠癌模型中,Met-EcN和抗PD-L1的联合治疗显著增加了瘤抑制和生存率.
- Met-EcN治疗增强了瘤微环境中的T细胞透和激活.
- 通过Met-EcN减少瘤细胞甲基化,激活cGAS-STING通路和先天免疫反应.
结论:
- 工程益生菌为瘤的向营养物质耗尽提供了一种新的策略.
- 与抗PD-L1免疫疗法相结合的Met-EcN显示出强大的抗瘤活性,并克服免疫抵抗.
- 这种方法调节瘤微环境,通过STING通路增强抗瘤免疫力.
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