自燃式纳米细菌生物混合物重编程 内瘤口腔微生物群免疫相互作用用于癌症免疫疗法
Yueru Pang1, Ruixin Kang1, Ziqi Shen1
1Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
概括
这项研究介绍了LYC@Bac,这是一种新的系统,可以消除像Fusobacterium nucleatum (Fn) 这样的免疫抑制细菌,并激活自然杀手 (NK) 细胞. 这种方法通过重编程瘤微环境 (TME) 来增强癌症免疫疗法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 微生物组研究 微生物组研究
背景情况:
- 癌症免疫疗法的有效性受到瘤微环境 (TME) 微生物群-免疫细胞相互作用的限制.
- 菌核素 (Fn) 抑制免疫细胞,特别是自然杀手 (NK) 细胞,阻碍抗瘤反应.
研究的目的:
- 开发一种生物混合系统 (LYC@Bac),同时针对Fn并激活TME内的NK细胞.
- 通过调节微生物群-免疫轴来增强癌症免疫疗法.
主要方法:
- 设计了一个纳米细菌生物混合系统 (LYC@Bac),结合了IL-15表达益生菌 (Bac) 和pH敏感的酶纳米粒子 (LYC).
- 利用酸性TME触发溶酶释放,溶解Fn并释放PAMP来激活树突细胞.
- 从溶解的Bac中促进IL-15的释放,通过mTOR途径激活NK细胞,升调NKG2D并增强细胞毒性作用因子分泌.
主要成果:
- LYC@Bac有效地消除了TME中的Fn,减少了免疫抑制.
- 激活的NK细胞表现出增强的抗瘤免疫力和对Fn.的抗菌功能.
- 建立了一个积极的反循环,加剧NK细胞介导的瘤清除和Fn根除.
结论:
- 该LYC@Bac生物混合系统精确地调节了内微生物群和免疫细胞的交叉通话.
- 这一策略提供了一种有前途的方法,通过向TME内的细菌和免疫成分来增强癌症免疫治疗结果.
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