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微波除触发了OX40L介导的TNFRSF4+Treg免疫抑制活性中断

Runqi Guo¹, Yufeng Wang^1,2, Jie Sun¹

¹Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Frontiers in immunology

|November 10, 2025

概括

微波切除 (MWA) 破坏了调节性T细胞 (Tregs),这些T细胞有助于瘤逃避免疫攻击. 这种通过OX40激动剂增强的方法,通过增强抗瘤反应,显示出癌症免疫治疗的前景.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物医学工程生物医学工程

背景情况:

调节性T细胞 (Tregs) 通过抑制抗瘤免疫力,对瘤免疫逃避至关重要.
向Treg免疫抑制活性是增强癌症免疫疗法的关键策略.
微波除 (MWA) 是一种热疗法,具有潜在的免疫调节作用.

研究的目的:

研究MWA对TNFRSF4+Tregs的免疫调节作用.
在MWA的背景下,探索OX40L/TNFRSF4信号轴作为治疗目标.
评估将MWA与OX40向疗法结合用于癌症治疗的潜力.

主要方法:

从C57BL/6小鼠中分离TNFRSF4+Tregs,并应用MWA模拟热应力.
在体外功能测定和体内LLC异种移植模型与OX40激动剂干预.
使用RT-qPCR,西斑,免疫组织化学和多色流细胞计学分析分子机制.

主要成果:

MWA诱导Tregs的表型转变,降低CTLA-4+和增加OX40L+子集,同时损害Treg抑制功能.
MWA增强了CD8+ T细胞细胞毒性,并增加了内CD8+/Treg比率,促进了抗瘤炎症状态.
MWA抑制了NF-κB/IκBα/TRAF6信号,其效果由OX40激动剂放大,表明OX40L的依赖性.

结论:

MWA有效地破坏了Treg介导的免疫抑制,可能是通过激活OX40L/TNFRSF4信号通路.
通过将平衡转向效应免疫细胞,MWA治疗有利于改变瘤的微环境.
将MWA与OX40向免疫疗法结合在一起,为癌症治疗提供了一种新且有前途的策略.

关键词:

CD8+ T 细胞 CD8+ T 细胞在TNFRSF4+ Treg中.微波除是微波除的一种方法.瘤免疫抑制可以抑制免疫.瘤微环境是一个微环境.

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