TMPRSS11D/ALR介导的ER压力调节了宫癌微环境中的骨髓原抑制细胞的功能
Sifang Feng1, Juan Zhao2, Ting Yang2
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
International immunopharmacology
|September 4, 2023
概括
跨膜血清蛋白酶11D (TMPRSS11D) 通过增强骨髓衍生抑制细胞 (MDSC) 免疫抑制,促进子宫癌免疫逃避. 沉默TMPRSS11D减少瘤生长和MDSC积累,提供了一个潜在的治疗点.
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:
- 骨髓系衍生抑制细胞 (MDSCs) 是瘤免疫逃避的关键参与者,特别是在宫癌中.
- 跨膜血清蛋白酶11D (TMPRSS11D) 在宫癌的免疫逃脱中的作用仍然在很大程度上未知.
- 了解TMPRSS11D在MDSC免疫抑制中的机制对于开发新型癌症疗法至关重要.
研究的目的:
- 研究TMPRSS11D对宫癌中MDSCs免疫抑制功能的调节机制.
- 为了确定TMPRSS11D是否影响MDSC介导的T细胞抑制.
- 在体内探索TMPRSS11D对子宫癌进展的影响.
主要方法:
- 在宫癌患者和良性瘤患者中对MDSC标记物和TMPRSS11D表达的比较分析.
- 在体外共同培养T细胞和MDSCs与TMPRSS11D敲除的T细胞和MDSCs的试验.
- 评估反应性氧物种 (ROS) 生产,T细胞增殖和IFN-γ水平.
- 在活体老鼠异种移植模型中,评估TMPRSS11D对瘤生长和MDSC透的影响.
主要成果:
- 恶性宫癌患者表现出较高的PMN-MDSC比例,免疫抑制因素和TMPRSS11DmRNA水平.
- 在MDSC中抑制TMPRSS11D降低了ROS的产生,并阻碍了它们对T细胞的免疫抑制能力.
- TMPRSS11D负调节了ALR表达,在MDSC中诱导了ER压力,并在体内促进了宫癌的生长.
结论:
- TMPRSS11D通过ALR降低调节诱导ER压力来增强宫癌中MDSC介导的免疫抑制.
- 准TMPRSS11D可能是一个有希望的策略,以克服免疫逃避和抑制子宫癌的进展.
- 对TMPRSS11D分子通路的进一步研究可能会揭示宫癌治疗的新疗法.
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