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Updated: Jun 26, 2025

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循环瘤透和CD8+T细胞的功能决定了免疫治疗的有效性

Chen Wang¹, Qun Zeng¹, Zeynep Melis Gül¹

¹Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.

|May 9, 2024

概括

瘤透的淋巴细胞对癌症免疫力至关重要, 免疫疗法等癌症治疗的时间与这些昼夜波动保持一致可以显著改善患者的治疗结果.

科学领域:

免疫学
时间生物学
癌症生物学

背景情况:

瘤透性淋巴细胞 (TIL),特别是CD8+ T细胞,对于抗瘤免疫和免疫治疗反应至关重要.
循环节律影响各种生理过程,但它们在瘤微环境中的作用尚未完全理解.

研究的目的:

调查瘤微环境中的TILs中昼夜振荡的存在和功能意义.
根据这些日常节奏,探索定时免疫疗法的治疗潜力.

主要方法:

使用流细胞计和单细胞RNA测序对小鼠和人类癌症的TIL群体 (包括CD8+T细胞) 进行分析.
在瘤微环境中评估白细胞透模式和内皮细胞钟功能.
评估在一天中不同时间使用的仿真抗原受体T细胞治疗和免疫检查点阻塞的疗效.
日间T细胞特征与患者存活率和治疗反应的相关性.

主要成果:

在小鼠和人类癌症中观察到TIL的质量和数量,包括CD8+T细胞.
这些振荡是由白细胞的内在昼夜时钟和依赖内皮细胞时钟的节律透驱动的.
当在一天中的特定时间进行治疗时,CAR T细胞治疗和免疫检查点阻塞的治疗效果得到增强.
在小鼠模型中,依赖于一天时间的T细胞特征预测了黑色素瘤患者的整体存活率,并与抗PD-1治疗反应相关.

结论:

循环动态在瘤微环境中发挥功能作用,影响免疫细胞透和抗瘤反应.
通过优化治疗时间来利用这些昼夜节律, 有望改善癌症免疫疗法.
这些发现强调了在未来的临床试验和患者护理策略设计中考虑时代生物学的重要性.

关键词:

其他:卡尔-治疗美国时间疗法昼夜时间免疫检查点封锁免疫学黑色素瘤瘤透白细胞

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