Single tumor-initiating cells evade immune clearance by recruiting type Ⅱ macrophages
Xiaocan Guo1Yang Zhao1Huan Yan1Yingcheng Yang2Shuying Shen3Xiaoming Dai1Xinyan Ji1Fubo Ji1Xing-Guo Gong3Li Li4Xueli Bai5Xin-Hua Feng1Tingbo Liang5Junfang Ji1Lei Chen2Hongyang Wang2Bin Zhao1
1. Life Sciences Institute and Innovation Center for Cell Signaling Network2. International Co-operation Laboratory on Signal Transduction,Eastern Hepatobiliary Surgery Institute,Second Military Medical University3. Institute of Biochemistry,College of Life Science4. Institute of Aging Research,Hangzhou Normal University5. Department of Hepatobiliary and Pancreatic Surgery and the Key Laboratory of Cancer Prevention and Intervention,The Second Affiliated Hospital,School of Medicine Zhejiang University
摘要：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 report,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 YAP is underlying macrophage recruitment by TICs.These results demonstrate for the first time that macrophages play a decisive role in the survival of single TIC in vivo,and provide a proof of principle for TIC elimination by targeting YAP or M2 macrophages.