瘤血管正常化和免疫刺激重编程的相互调节
Lin Tian1,2,3, Amit Goldstein1,2,4, Hai Wang1,2,4
1Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Nature
|April 4, 2017
概括
1型辅助细胞 (TH1) 对于正常化瘤血管至关重要,从而提高治疗效率. 这一发现揭示了TH1细胞在调节瘤血管和免疫反应中的新作用.
科学领域:
- 免疫学
- 癌症学
- 血管生物学
背景情况:
- 抗血管生成疗法可以增加瘤转移.
- 血管正常化,以改善输液和减少缺氧为特征,可能会解决这种悖论.
- 人们对船只规范化的监管机制仍然不太了解.
研究的目的:
- 研究T助手1 (TH1) 细胞在瘤血管正常化中的作用.
- 探索T淋巴细胞活动与血管正常化之间的关系.
- 确定TH1细胞是否可以减轻瘤缺氧.
主要方法:
- 对瘤基因表达的生物信息分析.
- 使用具有血管正常化或T淋巴细胞缺陷的小鼠模型.
- 研究了CD4+T淋巴细胞枯竭和激活 (通过免疫检查点阻塞) 对血管正常化的影响.
- 向患者衍生的异种移植模型进行采用TH1细胞转移.
主要成果:
- 与T淋巴细胞透和活性相关的血管正常化的基因表达特征.
- CD4+ T 淋巴细胞的消耗导致血管正常化受损,表明相互调节循环.
- 免疫检查点诱导的CD4+T淋巴细胞激活增强血管正常化.
- 分泌干扰素-γ的TH1细胞被确定为血管正常化的关键参与者.
- 在免疫缺陷小鼠中培养的患者衍生的异种移植瘤中,采用TH1转移减少了缺氧.
结论:
- 1型辅助细胞 (TH1) 在瘤血管正常化中起着至关重要的,以前未知的作用.
- TH1细胞是瘤血管和免疫系统之间的相互调节循环的组成部分.
- TH1细胞可以作为免疫检查点阻塞和抗血管生成治疗疗效的生物标志物和决定因素.
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