Tumor‐associated macrophages in liver cancer: From mechanisms to therapy

作者：Kun Cheng, Ning Cai, Jinghan Zhu, Xing Yang, Huifang Liang, Wanguang Zhang · 发表于：癌症：英文版 · 年份：2022 · DOI：10.1002/cac2.12345 · 被引用次数：456 · 研究领域：Immune cells in cancer、Immune Cell Function and Interaction、Phagocytosis and Immune Regulation

Multidimensional analyses have demonstrated the presence of a unique tumor microenvironment (TME) in liver cancer. Tumor-associated macrophages (TAMs) are among the most abundant immune cells infiltrating the TME and are present at all stages of liver cancer progression, and targeting TAMs has become one of the most favored immunotherapy strategies. In addition, macrophages and liver cancer cells have distinct origins. At the early stage of liver cancer, macrophages can provide a niche for the maintenance of liver cancer stem cells. In contrast, cancer stem cells (CSCs) or poorly differentiated tumor cells are key factors modulating macrophage activation. In the present review, we first propose the origin connection between precursor macrophages and liver cancer cells. Macrophages undergo dynamic phenotypic transition during carcinogenesis. In this course of such transition, it is critical to determine the appropriate timing for therapy and block specific markers to suppress pro-tumoral TAMs. The present review provides a more detailed discussion of transition trends of such surface markers than previous reviews. Complex crosstalk occurs between TAMs and liver cancer cells. TAMs play indispensable roles in tumor progression, angiogenesis, and autophagy due to their heterogeneity and robust plasticity. In addition, macrophages in the TME interact with other immune cells by directing cell-to-cell contact or secreting various effector molecules. Similarly, tumor cells combined w...