在皮肤状细胞癌中,miR-22通过激活JAK/STAT3信号来促进免疫抑制
Shukai Yuan1, Tong Zhu1, Jianan Wang1
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China.
Carcinogenesis
|July 19, 2023
概括
微RNA-22 (miR-22) 通过调节性T细胞 (Tregs) 创造免疫抑制性瘤微环境 (TME) 来促进皮肤状细胞癌 (cSCC). 向miR-22可能会克服cSCC的治疗耐药性.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 免疫疗法是高级皮肤状细胞癌 (cSCC) 唯一批准的全身治疗方法,但大约50%的患者表现出原发性耐药性或发展获得性耐药性.
- 了解驱动瘤微环境 (TME) 中免疫抑制的机制对于克服cSCC治疗耐药性至关重要.
研究的目的:
- 研究微RNA-22 (miR-22) 在促进cSCC发育和建立免疫抑制TME中的作用.
- 阐明miR-22在cSCC中促进免疫逃避的分子机制.
主要方法:
- 利用了cSCC的免疫能力强的基因工程小鼠模型.
- 进行了涉及miR-22,JAK/STAT3信号,SOCS3,化学基因 (CCL17,CCL20,CCL22) 和调控性T细胞 (Tregs) 的机制研究.
- 进行了转录基因分析和功能救援实验.
主要成果:
- miR-22通过诱导Tregs介导的免疫抑制以瘤细胞自主的方式促进cSCC的发展.
- miR-22通过抑制SOCS3来激活JAK/STAT3信号,从而增加化学激素分泌和Tregs招募.
- 对miR-22的表皮特异性淘汰减少了cSCC的进展,Tregs透,并增强了CD8+ T细胞的激活.
- 临床数据显示,SOCS3丰富度与cSCC中Tregs透之间存在负相关性,与升高的miR-22水平一致.
结论:
- miR-22在通过miR-22-SOCS3-JAK/STAT3-化学因子轴在cSCC中建立免疫抑制性TME中发挥着关键作用.
- 向miR-22是一个有希望的治疗策略,可以克服免疫逃逸并改善cSCC的治疗反应.
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