河马通路激酶 LATS1/2 抑制癌症免疫力
Toshiro Moroishi1, Tomoko Hayashi2, Wei-Wei Pan3
1Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|December 3, 2016
概括
希波路径,特别是大瘤抑制剂1和2 (LATS1/2) 激酶,意外地抑制了抗瘤免疫力. 抑制LATS1/ 2增强了免疫反应,导致瘤回归和改善了癌症疫苗的疗效.
科学领域:
- 免疫学
- 分子生物学
- 癌症学
背景情况:
- 免疫性较差的瘤细胞逃避宿主免疫监测,导致癌症的进展.
- 控制瘤免疫性的复杂机制尚不完全理解.
- 河马通路在调节抗瘤免疫力中的作用在很大程度上是未被探索的.
研究的目的:
- 调查河马在调节抗瘤免疫力中的作用.
- 为了确定是否准Hippo途径可以增强抗瘤免疫反应.
- 探索LATS1/2作为癌症免疫治疗的治疗点的潜力.
主要方法:
- 使用了三种小鼠综合性瘤模型 (B16,SCC7,4T1).
- 评估了删除瘤细胞中的大瘤抑制剂1和2 (LATS1/ 2) 激酶的影响.
- 研究了适应性免疫反应和细胞外囊分泌的作用.
- 分析了托尔类受体-MYD88/TRIF通路的激活.
主要成果:
- 在所有模型中,瘤细胞中的LATS1/ 2损失显著抑制了瘤生长.
- 由LATS1/ 2删除导致的瘤回归取决于适应性免疫反应.
- 瘤疫苗的疗效提高了LATS1/ 2的缺乏.
- 瘤细胞分泌了诱导I型干扰素反应的细胞外囊.
结论:
- 通过LATS1/2激酶,Hippo途径在抑制抗瘤免疫力方面发挥着至关重要的作用.
- 向LATS1/ 2可以增强瘤免疫性并促进免疫媒介的瘤破坏.
- 抑制LATS1/2是癌症免疫治疗的一个有前途的策略.
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