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黑色素瘤衍生的外体通过巨细胞的IRF7/I-IFN轴放大放射治疗诱导的膜效应

Lu Wang¹, Kangjie Shen¹, Zixu Gao¹

¹Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|January 29, 2024

概括

放射疗法 (RT) 通过释放瘤外体细胞来触发腹腔效应. 这些外体携带circPIK3R3,通过巨细胞激活和CD8+ T细胞反应增强抗瘤免疫力.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
分子生物学分子生物学

背景情况:

放射治疗 (RT) 可以诱导瘤回归超出照射区域 (腹膜效应).
精确的分子机制控制abscalcopal效应仍然在很大程度上未被阐明.
了解这些机制对于开发新型癌症免疫疗法至关重要.

研究的目的:

为了研究RT引起的abscopal效应的潜在机制.
通过RT探索瘤微环境 (TME) 调节的作用.
为了确定潜在的治疗策略,以增强abscopal效果.

主要方法:

在小鼠中建立了一种双重瘤模型 (皮下和肺转移).
利用单细胞RNA测序,免疫光学和流细胞测量来分析TME.
进行了体外测定 (露西法酶报告器,RNA拉低,FISH) 和体内研究.

主要成果:

RT显著抑制了瘤生长和肺转移,改善了TME.
RT诱导了含有circPIK3R3的瘤外体的释放,这些外体被巨细胞内化.
通过miR-872-3p/IRF7通路,circPIK3R3激活了巨细胞 (M1极化) 并促进了I型干扰素 (I-IFN) 的分泌.
I-IFN激活了CD8+T细胞中的JAK/STAT通路,增强了抗瘤细胞因子的分泌 (IFN-γ,GZMB).

结论:

瘤衍生的外生体通过将circPIK3R3转移到巨细胞中介于abscopal效应.
这一过程通过巨细胞极化和随后的CD8+ T细胞激活来增强抗瘤免疫力.
该circPIK3R3 / miR-872-3p / IRF7轴代表了调节对RT的免疫反应的新途径.

关键词:

在IRF7中,IRF7是什么?国际金融机构的I-IFN.这是一种abscopal效应.黑色素瘤是一种黑色素瘤.辐射疗法辐射疗法

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