Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

TY - JOUR

T1 - Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

AU - Casari, Martina

AU - Siegl, Dominik

AU - Deppermann, Carsten

AU - Schuppan, Detlef

N1 - Copyright © 2023 Casari, Siegl, Deppermann and Schuppan.

PY - 2023

Y1 - 2023

N2 - During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.

AB - During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.

KW - Humans

KW - Carcinoma, Hepatocellular/pathology

KW - Esophageal and Gastric Varices/metabolism

KW - Liver Neoplasms/pathology

KW - Gastrointestinal Hemorrhage

KW - Liver Cirrhosis

KW - Macrophages

KW - Fibrosis

U2 - 10.3389/fimmu.2023.1277808

DO - 10.3389/fimmu.2023.1277808

M3 - SCORING: Review article

C2 - 38116017

VL - 14

SP - 1277808

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -