TBK1-Zyxin信号控制着与瘤相关的巨细胞招募,以减轻抗瘤免疫力

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Updated: Jun 12, 2025

In Vitro Assay to Study Tumor-macrophage Interaction

In Vitro Assay to Study Tumor-macrophage Interaction

Published on: August 1, 2019

Ruyuan Zhou^1,2,3, Mengqiu Wang¹, Xiao Li¹

¹MOE Laboratory of Biosystems Homeostasis and Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.

The EMBO journal

|September 20, 2024

概括

天生的免疫传感途径通过激活TBK1激酶来调节巨细胞迁移,该激酶酸化Zyxin. 这种信号影响瘤相关的巨细胞局部化和抗瘤免疫力.

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:

机械线索对于组织中的细胞定位至关重要,影响瘤相关巨细胞 (TAMs).
天生的免疫传感途径,如cGAS-STING和RLR-MAVS影响癌症,但它们在巨细胞的居住和运动中的作用尚不清楚.

研究的目的:

研究由cGAS-STING/RLR-MAVS激活的TBK1激酶在调节巨细胞局部化和迁移中的作用.
探索这种信号通路对TAM和抗瘤免疫力的影响.

主要方法:

研究了由cGAS-STING或RLR-MAVS刺激的巨细胞中的TBK1激酶活性.
分析了齐辛酸化及其对焦点粘附和F-actin动态的影响.
研究了STING-TBK1-Zyxin信号在瘤内的TAMs中的作用.
评估了破坏这种途径对TAM群体和免疫治疗反应的影响.

主要成果:

TBK1激酶在S143处直接酸化Zyxin,促进其招募到焦点粘附.
这种酸化导致F-actin重组,并减少了巨细胞的迁移.
内STING-TBK1-Zyxin信号存在于TAM中,并影响抗瘤免疫力.
破坏这种途径减少了TAMs并增强了PD-1免疫疗法.

结论:

在控制巨细胞组织局部化方面,确定了先天免疫感应通路的新功能.
STING-TBK1-Zyxin轴调节TAM行为,并影响抗瘤免疫疗法的疗效.
这些发现提供了对调节巨细胞局部化的见解,以改善癌症治疗.

关键词:

抗瘤免疫抗瘤免疫细胞移动性细胞移动性在TBK1中,与瘤相关的巨细胞 cGAS-STING 的使用情况.

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