Tumor-associated macrophages in liver cancer: From mechanisms to therapy.
Tumor-associated macrophages in liver cancer: From mechanisms to therapy.
复制标题
肝癌中的肿瘤相关巨噬细胞：从机制到治疗。
DOI：
10.1002/cac2.12345
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发表时间：
2022-11
影响因子：
16.2
通讯作者：
Zhang, Wanguang
中科院分区：
文献类型：
--
作者：
Cheng, Kun;Cai, Ning;Zhu, Jinghan;Yang, Xing;Liang, Huifang;Zhang, Wanguang
关键词：
多维分析表明，肝癌中存在独特的肿瘤微环境（TME）。肿瘤相关巨噬细胞（TAM）是浸润TME的最丰富的免疫细胞之一，存在于肝癌进展的所有阶段，靶向TAM已成为最受欢迎的免疫治疗策略之一。此外，巨噬细胞和肝癌细胞具有不同的起源。在肝癌的早期阶段，巨噬细胞可以为肝癌干细胞的维持提供一个小生境。相比之下，癌症干细胞（CSC）或低分化肿瘤细胞是调节巨噬细胞活化的关键因素。本文首次提出前体巨噬细胞与肝癌细胞的起源联系。巨噬细胞在癌变过程中发生动态表型转变。在这种转变过程中，关键是要确定治疗的适当时机，并阻断特异性标志物以抑制促肿瘤TAM。与之前的评论相比，本评论对此类表面标记物的转变趋势进行了更详细的讨论。TAM与肝癌细胞之间存在复杂的串扰。由于TAM的异质性和强大的可塑性，它们在肿瘤进展、血管生成和自噬中起着不可或缺的作用。此外，TME中的巨噬细胞通过引导细胞间接触或分泌各种效应分子与其他免疫细胞相互作用。类似地，肿瘤细胞与其他免疫细胞结合可以驱动巨噬细胞募集和极化。尽管TAMs研究取得了最新成就和治疗策略的进步，但目前缺乏对肝癌中巨噬细胞与癌细胞或免疫细胞之间通讯的全面讨论。本文综述了TAM与肝癌细胞之间的相互作用（从细胞起源到成熟）、最新的治疗策略（包括嵌合抗原受体巨噬细胞）以及针对肝细胞癌（HCC）和肝内胆管细胞癌（iCCA）的关键临床试验，为TAM作为治疗肝癌患者的潜在靶点的进一步临床研究提供理论基础。
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 with other immune cells can drive macrophage recruitment and polarization. Despite the latest achievements and the advancements in treatment strategies following TAMs studies, comprehensive discussions on the communication between macrophages and cancer cells or immune cells in liver cancer are currently lacking. In this review, we discussed the interactions between TAMs and liver cancer cells (from cell origin to maturation), the latest therapeutic strategies (including chimeric antigen receptor macrophages), and critical clinical trials for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) to provide a rationale for further clinical investigation of TAMs as a potential target for treating patients with liver cancer.
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DOI：
10.1002/hep.30249
发表时间：
2019-03
期刊：
Hepatology (Baltimore, Md.)
影响因子：
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发表时间：
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期刊：
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影响因子：
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影响因子：
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DOI：
10.1073/pnas.1113744109
发表时间：
2012-02-14
影响因子：
11.1
作者：
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通讯作者：
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