CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：COUP-TFII-mediated reprogramming of the vascular endothelium counteracts tumor immune evasion.
COUP-TFII-mediated reprogramming of the vascular endothelium counteracts tumor immune evasion.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
肿瘤组织中T细胞稀缺对癌症免疫治疗构成了关键挑战。在此，我们操控肿瘤血管系统——免疫细胞运输的重要调节者——以在“冷”肿瘤中重新激发抗肿瘤T细胞反应。我们发现，静脉发育的主转录因子COUP-TFII在泛内皮细胞中的异位表达可诱导肿瘤内皮细胞中毛细血管后微静脉的分子程序。微静脉重编程选择性促进T细胞向肿瘤内募集，抑制乳腺癌和胰腺癌小鼠模型中的肿瘤生长，并使肿瘤对免疫检查点阻断和过继性T细胞转移治疗敏感。机制研究表明，抗肿瘤T细胞募集的增强和肿瘤抑制由COUP-TFII诱导的血管黏附受体所介导。我们的研究支持血管内皮细胞在调控肿瘤免疫逃逸中的关键作用，并提出微静脉重编程作为增强抗肿瘤免疫和免疫治疗的治疗策略。
T cell scarcity in tumor tissues poses a critical challenge to cancer immunotherapy.
Here we manipulate the tumor vasculature, an essential regulator of immune cell trafficking, to reinvigorate anti-tumor T cell responses in "cold" tumors.
We show that ectopic pan-endothelial expression of COUP-TFII, a master transcription factor for venous development, induces molecular programs of post-capillary venules in tumor endothelium.
Venular reprogramming selectively promotes T cell recruitment into tumors, inhibits tumor growth in mouse models of breast and pancreatic cancers, and sensitizes tumors to immune checkpoint blockade and adoptive T cell transfer therapies. Mechanistic studies show that enhanced recruitment of anti-tumor T cells and tumor inhibition are mediated by COUP-TFII-induced vascular adhesion receptors.
Our study supports a pivotal role of vascular endothelial cells in governing tumor immune evasion, and proposes venular reprogramming as a therapeutic strategy to bolster anti-tumor immunity and immunotherapy.
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
MEMBER ACCOUNT
登录成功会直接打开下一页。
