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多金属纳米片通过增强cGAS-STING天生的激活和适应性免疫反应来重塑免疫抑制瘤的微环境

Yuxuan Peng^1,2, Shuang Liang^1,2, Dan Liu^1,2

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 science (Weinheim, Baden-Wurttemberg, Germany)

|August 9, 2024

概括

这项研究引入了含的多层双氧化物 (Mn-LDH) 来逆转免疫抑制瘤微环境 (TME). Mn-LDH通过激活免疫细胞和抑制瘤生长来增强抗瘤免疫力,提供了一个有前途的癌症免疫治疗候选人.

科学领域:

生物医学工程生物医学工程
免疫学免疫学免疫学
材料科学材料科学材料科学

背景情况:

瘤微环境 (TME) 具有高度的免疫抑制作用,阻碍了针对癌症的有效免疫反应.
恢复免疫监测需要TME的正常化,以促进抗瘤免疫力.

研究的目的:

开发一种新型的免疫治疗剂,辅助层状双氧化物 (Mn-LDH),用于逆转TME诱导的免疫抑制.
研究Mn-LDH增强针对瘤的先天性和适应性免疫反应的机制.

主要方法:

Mn-LDH是使用一步热水方法合成的.
评估Mn-LDH在TME中的质子中和氧气生产能力.
评估Mn-LDH激活干扰素基因合成刺激酶 (STING) 途径并维持CD8+ T细胞细胞毒性的能力.
分析Mn-LDH对免疫细胞透 (树突细胞,巨细胞,T细胞) 和瘤生长抑制的影响.
研究光热转换效应,以提高治疗效果.

主要成果:

Mn-LDH有效中和质子,并在TME中产生氧气.
释放的Mn2+和Mg2+离子激活STING通路并保持CD8+T细胞功能.
局部管理的Mn-LDH促进一个"热"TME与增加的免疫细胞的存在.
观察到主要和远端瘤生长的显著抑制.
光热疗法结合Mn-LDH的使用,在已建立的瘤中显示出增强的疗效.

结论:

Mn-LDH显示出强大的TME调节能力,恢复抗瘤免疫力.
质子中和和氧气生成的双重作用,加上离子释放,驱动免疫激活.
Mn-LDH代表了下一代癌症免疫治疗的有希望的临床候选人,特别是与光热疗法相结合时.

关键词:

在cGAS-STING信号通道中.癌症免疫疗法免疫疗法免疫抑制性瘤微环境有层的双氧化.

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