细胞衍生的细胞外囊泡损害了巨细胞中的cGAS-STING活性
Stoyan Tankov1,2, Marija Petrovic3, Marc Lecoultre1,2
1Translational Research Center in Onco-Hematology (CRTOH), Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Cell communication and signaling : CCS
|February 23, 2024
概括
低毒性质母细胞细胞释放细胞外囊泡 (EVs),携带微RNA (miRNAs),抑制巨细胞的抗瘤免疫力. 这种由EV介导的miR-25/93的转移会损害T细胞的反应,从而导致免疫抑制性瘤微环境.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 像质母细胞瘤 (GBM) 这样的固体瘤有缺氧区域,与预后不佳和免疫抑制有关.
- 细胞外囊泡 (EVs) 可以在细胞之间传输分子载荷,在瘤微环境中潜在地调解细胞间通信.
研究的目的:
- 为了调查缺氧癌细胞是否使用EVs在正常的条件下抑制巨细胞功能.
- 阐明EV介导的微RNA转移在质母细胞瘤相关免疫抑制中的作用.
主要方法:
- 通过超离心,电子显微镜和NTA从GBM细胞培养物中分离和特征化EV.
- 使用qPCR和显微镜确认了巨细胞的EV吸收和miR-25/93的转移.
- 通过转录分析和功能测定,评估了miR-25/93对巨分极和T细胞反应的影响.
主要成果:
- 缺氧增加了GBM细胞的EV释放,并在细胞和EV中调高了miR-25/93.
- 携带miR-25/93的GBM衍生的EV被巨细胞吸收,损害了cGAS-STING通路的激活,并减少了I型IFN分泌.
- 用EV治疗的巨细胞显示M1极化标记物减少,以及吸引和重新激活抗瘤T细胞的能力受损.
结论:
- 缺氧诱导的EVs从GBM细胞输出miR-25/93到巨细胞,促进T细胞介导的免疫抑制.
- 这种EV-miRNA机制突出了瘤微环境中广泛免疫抑制的途径.
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