Yang Wan-Li, Yang Chao, Pang Nan, Yu Rui-Hua, Tong Kui-Yuan, Jiang Feng
Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai 202150, China.
Faculty of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, Jiangsu, China.
Cell Immunol. 2025 Mar-Apr;409-410:104917. doi: 10.1016/j.cellimm.2025.104917. Epub 2025 Jan 17.
The peritoneal cavity (PerC) is a discrete anatomical compartment housing diverse peritoneal macrophage subpopulations. Nonetheless, there exists a paucity of knowledge concerning the distinct functions of these subpopulations in the context of hepatocellular carcinoma (HCC) and their evolution throughout tumor advancement. This investigation seeks to analyze the characteristics of two principal peritoneal macrophage subpopulations, specifically large peritoneal macrophage (LPM) and small peritoneal macrophage (SPM), in the context of HCC. The results of our research indicate a significant decrease in the proportion of LPM during the progression of HCC, accompanied by an increase in the quantity of SPM. Furthermore, SPM found in ascites exhibited a macrophage phenotype that supports tumor growth in HCC. Importantly, the dynamic decrease of LPM in murine models following lipopolysaccharide (LPS) stimulation led to a decrease in survival rate, highlighting the critical role of the altered LPM to SPM ratio in HCC survival. By employing clodronate liposomes (CL) to deplete peritoneal macrophage in murine models, followed by the adoptive transfer of LPM, we effectively prolonged the survival of HCC and attenuated tumor progression. Our results suggest that a decrease in the LPM to SPM ratio correlates with increased mortality in the HCC model. On the contrary, the maintenance of a high ratio of LPM to SPM has shown a positive effect on HCC survival. These findings have enhanced our understanding of the complex interaction between different subpopulations of peritoneal macrophage in the development of HCC. Furthermore, these results have important implications for the development of novel therapeutic strategies.
腹膜腔（PerC）是一个容纳多种腹膜巨噬细胞亚群的离散解剖腔隙。然而，关于这些亚群在肝细胞癌（HCC）背景下的独特功能及其在肿瘤进展过程中的演变，目前仍知之甚少。本研究旨在分析HCC背景下两种主要腹膜巨噬细胞亚群，即大腹膜巨噬细胞（LPM）和小腹膜巨噬细胞（SPM）的特征。我们的研究结果表明，在HCC进展过程中，LPM的比例显著下降，同时SPM的数量增加。此外，腹水中发现的SPM表现出支持HCC肿瘤生长的巨噬细胞表型。重要的是，脂多糖（LPS）刺激后小鼠模型中LPM的动态减少导致存活率下降，突出了HCC存活中LPM与SPM比例改变的关键作用。通过使用氯膦酸盐脂质体（CL）耗尽小鼠模型中的腹膜巨噬细胞，然后过继转移LPM，我们有效地延长了HCC小鼠的生存期并减弱了肿瘤进展。我们的结果表明，HCC模型中LPM与SPM比例的降低与死亡率增加相关。相反，维持高比例的LPM与SPM对HCC存活显示出积极作用。这些发现增进了我们对腹膜巨噬细胞不同亚群在HCC发生发展中复杂相互作用的理解。此外，这些结果对新型治疗策略的开发具有重要意义。
