在白血病细胞中LILRB4信号介导T细胞抑制和瘤透
Mi Deng1, Xun Gui2, Jaehyup Kim3
1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature
|October 19, 2018
概括
这种受体有助于瘤扩散并抑制T细胞. 阻断LILRB4可用于治疗单细胞急性髓性白血病 (AML).
科学领域:
- 免疫学
- 癌症学
- 分子生物学
背景情况:
- 免疫检查点阻塞疗法对某些癌症有效,但不对白血病有效.
- 白血病可能具有独特的免疫逃避机制.
- 白血病细胞上的免疫抑制受体可能会启动促进瘤的信号.
研究的目的:
- 研究LILRB4在单细胞白血病中的作用.
- 阐明 LILRB4 影响白血病进展和免疫抑制的信号通路.
主要方法:
- 使用小鼠模型和人类白血病细胞.
- 分析了涉及APOE,SHP-2,UPAR和ARG1的LILRB4信号通路.
- 评估LILRB4删除和抗体阻断对白血病发展的影响.
主要成果:
- 在急性髓性白血病 (AML) 中,LILRB4 支持瘤细胞透,抑制T细胞活性.
- 对于这些影响来说,LILRB4通路 (APOE,LILRB4,SHP-2,UPAR,ARG1) 是至关重要的.
- 在模型中,LILRB4的删除或阻断显著阻碍了AML的发展.
结论:
- 在单细胞白血病中,LILRB4调节瘤侵袭和免疫抑制.
- LILRB4形成了一个免疫抑制的微环境,促进白血病的进展.
- 在单细胞AML治疗中,LILRB4是潜在的治疗点.
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