癌症起始细胞如何逃避免疫监视:募集M2型巨噬细胞
  • II型巨噬细胞(M2)可以通过抑制免疫清除,刺激血管生成及细胞增殖来促进肿瘤发生;
  • M2被发现在肝脏肿瘤起始细胞附近富集,但其具体作用还不清楚;
  • 本研究通过尾静脉注射质粒,从而在肝细胞中过表达YAP基因来研究YAP及M2在肝脏肿瘤发生中的作用;
  • 结果发现:YAP过表达可以促进肝脏肿瘤的发生,YAP通过激活CCL2及CSf1的表达来招募大量的M2;
  • 富集的M2,通过帮助肿瘤细胞逃避免疫清除来促进肿瘤发生。
关键字
延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
图片

Single tumor-initiating cells evade immune clearance by recruiting type II macrophages

单个肿瘤起始细胞通过招募II型巨噬细胞来逃避免疫清除

10.1101/gad.294348.116

2017-02-21, Article

Abstract & Authors:展开

Abstract:收起
Tumor infiltrated type II (M2) macrophages promote tumorigenesis by suppressing immune clearance, promoting proliferation, and stimulating angiogenesis. Interestingly, macrophages were also found to enrich in small foci of altered hepatocytes containing liver tumor-initiating cells (TICs). However, whether and how TICs specifically recruit macrophages and the function of these macrophages in tumor initiation remain unknown due to technical difficulties. In this study, by generating genetically defined liver TICs, we demonstrate that TICs actively recruit M2 macrophages from as early as the single-cell stage. Elimination of TIC-associated macrophages (TICAMs) abolishes tumorigenesis in a manner dependent on the immune system. Mechanistically, activation of the Hippo pathway effector Yes-associated protein (YAP) underlies macrophage recruitment by TICs. These results demonstrate for the first time that macrophages play a decisive role in the survival of single TICs in vivo and provide a proof of principle for TIC elimination by targeting YAP or M2 macrophages.

First Authors:
Xiaocan Guo

Correspondence Authors:
Bin Zhao

All Authors:
Xiaocan Guo,Yang Zhao,Huan Yan,Yingcheng Yang,Shuying Shen,Xiaoming Dai,Xinyan Ji,Fubo Ji,Xing-Guo Gong,Li Li,Xueli Bai,Xin-Hua Feng,Tingbo Liang,Junfang Ji,Lei Chen,Hongyang Wang,Bin Zhao

评论