What will a cell do if it mutates into the first cancer cell? Scientists at Zhejiang University discover that it will ‘recruit’ macrophages as a joint culprit. They will play a crucial role in the survival of liver tumor-initiating cells (TICs) and the incidence of liver cancer.
Recently, the research team led by Zhao Bin in the Life Sciences Institute, Zhejiang University, revealed for the first time that TICs can evade immune clearance by means of a series of activities the minute liver cancer is contracted. These findings will produce an appreciable impact on the understanding of the mechanisms for liver cancer and the development of relevant immunotherapy. This research is published in Genes & Development, a top journal in the field of life sciences.
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 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, researchers 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.
Tumor immunotherapy has been one of the primary issues in cancer research in recent years. Experts in this field believe that Zhao Bin’s findings provide significant implications for the elimination or prevention of tumor through the activation of the immune system.