一个促进T细胞从淋巴结出口的自程序控制了对免疫检查点阻塞反应的反应
Diede Houbaert1, Apostolos Panagiotis Nikolakopoulos2, Kathryn A Jacobs3
1Cell Death Research and Therapy Group, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; VIB Center for Cancer Biology Research (CCB), Leuven, Belgium.
Cell reports
|March 30, 2024
概括
淋巴内皮细胞 (LEC) 中的自对于指导淋巴结内T细胞运动至关重要. 扰乱LEC自会通过阻碍T细胞招募和免疫疗法的有效性来降低抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 淋巴内皮细胞 (LECs) 调节淋巴结 (LNs) 中的免疫细胞贩运.
- 了解LEC对T细胞动态的控制对于免疫疗法至关重要,但仍然不完整.
- 对瘤的外围T细胞招募对于抗癌免疫反应至关重要.
研究的目的:
- 研究LEC中自的作用,以控制稳定状态和瘤条件下的T细胞动态.
- 阐明LECs影响T细胞贩运和相互作用的分子机制.
- 确定LEC自对抗瘤免疫力和免疫治疗疗效的影响.
主要方法:
- 在小鼠体内成像和免疫表型.
- 自基因Atg5.5的LEC特有的删除.
- 单细胞RNA测序的瘤排水LNs.
- 评估T细胞和自然杀手细胞透和免疫治疗反应.
主要成果:
- 特定于LEC的Atg5删除改变了淋巴细胞的定位和在LNs中的持久性.
- 在LEC中ATG5的丧失导致LEC表型变化和淋巴细胞贩运途径的变化.
- 损坏的LEC自阻止了瘤透免疫细胞的招募,并废除了免疫疗法反应.
结论:
- LEC自对于维持T细胞动态和免疫监测至关重要.
- 一个LEC-自程序对于有效的抗瘤免疫和免疫治疗至关重要.
- 准LEC自可能是增强癌症免疫疗法的新策略.
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