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血管内皮的COUP-TFII介导的重编程可以抵消瘤免疫逃避

Yu Zhu^1,2, Kevin F Brulois^3,4, Thanh T Dinh^3,4,5

¹Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. zhuyu88@stanford.edu.

Nature communications

|August 12, 2025

概括

通过表达静脉发育的基因COUP-TFII来操纵瘤血管,增强T细胞进入瘤. 这种方法抑制了瘤的生长,并在临床前癌症模型中提高了免疫治疗的有效性.

科学领域:

免疫学免疫学免疫学
血管生物学血管生物学
癌症研究癌症研究

背景情况:

瘤中的T细胞稀缺性阻碍了有效的癌症免疫疗法.
瘤血管系统在调节免疫细胞透方面发挥着至关重要的作用.
在"寒冷"瘤中开发增强抗瘤T细胞反应的策略至关重要.

研究的目的:

研究瘤血管结构的操纵,以改善抗瘤T细胞的反应.
确定诱导瘤内皮中的静脉发育程序是否可以增强T细胞的招募.
评估静脉重编程与现有的癌症免疫疗法相结合的治疗潜力.

主要方法:

在瘤内皮细胞中表达COUP-TFII (转录因子) 的宫外表达.
使用乳腺癌和胰腺癌的小鼠模型分析T细胞贩运到瘤中的情况.
评估瘤生长抑制和对免疫检查点阻塞和采用T细胞转移疗法的敏感性.
机制研究以确定COUP-TFII诱导的介导T细胞招募的因素.

主要成果:

宫外全内皮表达COUP-TFII重编程瘤内皮向静脉分子特征.
这种静脉重编程有选择地增强了T细胞在瘤中的招募.
在临床前癌症模型中,COUP-TFII诱导抑制了瘤生长.
重编程的瘤对免疫检查点阻塞和采用性T细胞转移的敏感性增加.

结论:

瘤血管内皮细胞是调节瘤免疫逃逸的关键.
通过COUP-TFII进行静脉重编程可以增强抗瘤T细胞的反应.
静脉重编程是一种有前途的治疗策略,可以增强抗瘤免疫力和免疫疗法的有效性.

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