由于原纤维密度和对齐而导致的矩阵硬化调节了YAP介导的T细胞免疫抑制
Jiranuwat Sapudom1, Aseel Alatoom2, Paul Sean Tipay3
1Laboratory for Immuno Bioengineering Research and Applications, Division of Engineering, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.
Biomaterials
|October 26, 2024
概括
较硬的瘤通过改变细胞外基质 (ECM) 来抑制T细胞免疫反应. 准YAP信号可以恢复T细胞功能,提高癌症免疫治疗在这些具有挑战性的环境中的有效性.
科学领域:
- 免疫学 免疫学 免疫学
- 生物材料科学 生物材料科学
- 癌症生物学 癌症生物学
背景情况:
- T细胞对于免疫反应至关重要,并适应机械信号.
- 癌症病理通常涉及由于改变的原体而导致更硬的细胞外基质 (ECM).
- ECM的刚性和对齐可以显著影响T细胞功能和免疫监测.
研究的目的:
- 调查ECM密度和纤维状线如何影响T细胞行为.
- 阐明YAP信号在调解ECM诱导的T细胞抑制中的作用.
- 探索克服癌症中ECM介导免疫抑制的治疗策略.
主要方法:
- 使用了三维 (3D) 原基质,控制密度和纤维的对齐.
- 评估了T细胞激活,细胞因子产生,增殖,活性蛋白水平和迁移.
- 研究了YAP信号抑制对T细胞响应在刚性ECM的影响.
主要成果:
- 增加的ECM刚度 (密度或对齐) 抑制了T细胞激活,细胞因子产生和扩散,主要通过YAP信号传递.
- 矩阵对齐,不同于密度,改变T细胞迁移和降低活性蛋白水平.
- 抑制YAP信号传递恢复了T细胞激活和免疫反应在刚性ECM.
结论:
- ECM的刚性和对齐显著损害T细胞功能,影响抗瘤免疫力.
- YAP信号传递是ECM诱导的T细胞抑制的关键媒介.
- 针对YAP信号提供了一个有希望的策略,以提高免疫疗法在硬的瘤微环境中的疗效.
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