The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities

Frontiers in Molecular Biosciences

Molecular Biosciences

Marlene Sophia Kohlhepp¹  Frank Tacke¹  Hanyang Liu¹  Adrien Guillot² 

[1] Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany;null;

关键词: liver macrophages;    hepatocellular carcinoma;    immunotherapy;    non-alcoholic steatohepatitis;    monocytes;    tumor-associated macrophages;   

DOI  :  10.3389/fmolb.2023.1129831

 received in 2022-12-22, accepted in 2023-01-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

Chronic liver diseases from varying etiologies generally lead to liver fibrosis and cirrhosis. Among them, non-alcoholic fatty liver disease (NAFLD) affects roughly one-quarter of the world population, thus representing a major and increasing public health burden. Chronic hepatocyte injury, inflammation (non-alcoholic steatohepatitis, NASH) and liver fibrosis are recognized soils for primary liver cancer, particularly hepatocellular carcinoma (HCC), being the third most common cause for cancer-related deaths worldwide. Despite recent advances in liver disease understanding, therapeutic options on pre-malignant and malignant stages remain limited. Thus, there is an urgent need to identify targetable liver disease-driving mechanisms for the development of novel therapeutics. Monocytes and macrophages comprise a central, yet versatile component of the inflammatory response, fueling chronic liver disease initiation and progression. Recent proteomic and transcriptomic studies performed at singular cell levels revealed a previously overlooked diversity of macrophage subpopulations and functions. Indeed, liver macrophages that encompass liver resident macrophages (also named Kupffer cells) and monocyte-derived macrophages, can acquire a variety of phenotypes depending on microenvironmental cues, and thus exert manifold and sometimes contradictory functions. Those functions range from modulating and exacerbating tissue inflammation to promoting and exaggerating tissue repair mechanisms (i.e., parenchymal regeneration, cancer cell proliferation, angiogenesis, fibrosis). Due to these central functions, liver macrophages represent an attractive target for the treatment of liver diseases. In this review, we discuss the multifaceted and contrary roles of macrophages in chronic liver diseases, with a particular focus on NAFLD/NASH and HCC. Moreover, we discuss potential therapeutic approaches targeting liver macrophages.

【 授权许可】

Unknown   
Copyright © 2023 Kohlhepp, Liu, Tacke and Guillot.