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凝固蛋白酶调节瘤微环境中的核酸吸收和cGAS-STING-IFN诱导

Petra Wilgenbus¹, Jennifer Pott¹, Sven Pagel¹

¹Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center, Mainz, Germany.

|July 22, 2025

概括

恶性瘤通过单细胞上的X因子 (FX) 促进血栓形成,抑制抗瘤免疫力. 抑制FXa可以增强免疫反应,并与免疫疗法协同,以更好地治疗癌症.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
血液学血液学血液学

背景情况:

恶性瘤涉及免疫细胞,血小板和凝血之间的复杂相互作用,影响血栓形成和转移.
瘤微环境 (TME) 中的血小板和凝血因子可以促进瘤生长和免疫抑制.

研究的目的:

调查凝血因子X (FX) 对TME单细胞的作用.
探索FXa信号对免疫细胞和抗瘤反应的影响.
评估FXa抑制作为癌症免疫治疗中的潜在治疗策略.

主要方法:

对癌症患者和瘤携带小鼠的FX表达单细胞和血小板聚合物的分析.
使用骨髓细胞特异性基因删除的FX和PAR2信号封锁.
评估免疫细胞功能,包括抗原吸收和T细胞反应,以应对FXa抑制.
研究FXa抑制剂和免疫检查点抑制剂之间的协同作用.

主要成果:

增加的FX表达单细胞形成血小板聚合体,抑制单细胞分化和抗原呈现.
骨髓细胞FXa-PAR2信号缺陷增强了APC并激活了cGAS-STING-IFN-I通路,扩大了耗尽的CD8+ T细胞.
药理性FXa阻断扩大T细胞原始化和与免疫检查点抑制剂协同作用,改善抗瘤免疫力.

结论:

在TME中,FXa对髓状细胞的信号抑制了抗瘤免疫反应.
抑制FXa可以恢复免疫细胞功能并增强抗瘤免疫力.
抑制FXa具有与癌症免疫疗法结合治疗的翻译潜力.

关键词:

癌症免疫疗法癌症免疫疗法凝血是凝固的过程.免疫学免疫学免疫学在瘤学瘤学.血小板是血小板的组成部分.血管生物学血管生物学

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