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免疫刺激剂水凝导向瘤微环境重编程以有效地增强巨介导细胞化作用,用于全身癌症免疫疗法
Jun-Long Liang1, Xiao-Kang Jin1, Guo-Feng Luo2
1Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
ACS nano
|August 16, 2023
概括
这项研究设计了一种水凝,以增强巨细胞介导细胞化 (MMCP) 用于癌症免疫治疗. 水凝有效地准瘤细胞,并重塑瘤微环境 (TME),以提高抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
背景情况:
- 巨细胞媒介细胞化 (MMCP) 对于抗瘤免疫疗法至关重要.
- 瘤细胞避开了细胞分裂,瘤微环境 (TME) 是免疫抑制的,阻碍了MMCP.
- 开发克服这些障碍的策略对于有效的癌症免疫疗法至关重要.
研究的目的:
- 设计一种能够促进MMCP的新型水凝 (TCCaGM).
- 研究水凝调节TME并增强抗瘤免疫反应的能力.
- 评估水凝与PD-1抗体的联合治疗,以改善癌症免疫疗法.
主要方法:
- 通过使用CaCO3纳米粒子,设计了一种水凝 (TCCaGM) 封装颗粒细胞 - 巨细胞殖民地刺激因子 (GM-CSF) 和一个纳米平台 (TCCaN) 带有突尼胺素 (Tuni) 和催化酶 (CAT).
- 评估了水凝对缺氧/酸性TME的影响,对"吃我"信号 (calreticulin,CRT) 的上调和对瘤细胞"不要吃我"信号 (CD47) 的下调.
- 评估了树突细胞 (DCs) 的招募和激活,瘤相关巨细胞 (TAMs) 向M1-类表型的极化,以及CD8+ T细胞的反应.
- 研究了水凝与PD-1抗体 (αPD-1) 对全身抗瘤免疫,瘤控制,转移和复发的协同作用.
主要成果:
- 工程水凝 (TCCaGM) 有效地缓解了缺氧/酸性TME.
- 观察到CRT的上调和CD47的下调在瘤细胞上,促进细胞化.
- 水凝增强了DC招募/激活,并促进了TAMs向抗瘤M1表型的两极分化.
- 与αPD-1的联合治疗显著增强了全身抗瘤免疫力,控制了瘤生长,并抑制了转移和复发.
结论:
- TCCaGM水凝是一种增强MMCP和克服TME诱导的免疫抑制的有希望的策略.
- 工程水凝有效地重新编程TME以促进抗瘤免疫反应.
- 与αPD-1抗体的组合疗法为具有长期效果的高性能抗瘤免疫疗法提供了一种强有力的方法.
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