瘤微环境响应纳米粒子放大癌症免疫疗法的STING信号通路
Dan Liu1,2, Shuang Liang1,2, Kongshuo Ma1,2
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Advanced materials (Deerfield Beach, Fla.)
|September 19, 2023
概括
响应瘤微环境的纳米颗粒激活STING和TLR4通路,增强I型干扰素的产生和T细胞的反应. 这种方法克服了免疫抑制,提高了癌症免疫疗法的疗效,产生了持久的抗瘤记忆.
科学领域:
- 免疫学 免疫学 免疫学
- 纳米技术纳米技术
- 在瘤学瘤学.
背景情况:
- 癌症免疫疗法受到不足的STING通路激活和免疫抑制瘤微环境的限制.
- 向STING和Toll-like受体4 (TLR4) 提供了增强抗瘤免疫力的潜力.
研究的目的:
- 开发适应瘤微环境 (TME) 的纳米粒子 (PMM NPs),同时激活STING和TLR4.
- 调查PMMNP克服TME介导免疫抑制和增强自适应性免疫反应的潜力.
- 在临床前癌症模型中评估PMMNP与抗PD-1疗法相结合的协同效果.
主要方法:
- 设计和合成TME响应纳米粒子 (PMM NP).
- 在体外和体内评估STING和TLR4激活.
- 对细胞因子分泌 (例如,IFN-β) 和免疫细胞群 (T细胞,巨细胞) 的分析.
- 在结直肠和乳腺癌模型中评估治疗疗效,包括与抗PD-1的联合治疗.
主要成果:
- 通过TLR4介导的NF-κB信号传递,PMM NPs显著增强了STING激活,I型干扰素 (IFN-β) 的分泌量增加了4.0倍.
- 通过减少调节性T细胞和两极化M2巨细胞到M1,促进免疫支持环境,PMMNP调节了TME.
- 与PMMNP和抗PD-1抗体的联合治疗在炎症和非炎症瘤模型中都显示出协同效果.
- 挑战无瘤动物诱导了完全的瘤排斥,表明系统性抗瘤记忆的发展.
结论:
- 响应TME的纳米粒子为STING激活的时空编排提供了一种新的策略.
- 这种方法通过克服免疫抑制和促进自适应性免疫反应,有效增强抗瘤免疫力.
- PMM NPs代表了下一代癌症免疫治疗的有希望的临床候选人,可能导致持久的反应和记忆.
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