Beyond cancer: CAR-T cells redefining liver disease therapy

Hepatic fibrosis remains a major unmet clinical challenge worldwide.Liver diseases can arise from a variety of etiologies with overlapping yet distinct pathogenic pathways.These etiologies include metabolic dysfunction-associated steatohepatitis (MASH), chronic viral hepatitis particularly hepatitis B and C, alcohol-associated liver disease (ALD), autoimmune diseases, biliary diseases, and drug-induced liver injury (1).Repeated or sustained hepatic injury from these insults drives fibrosis progression, which can culminate in cirrhosis-a late-stage condition characterized by extensive scarring, regenerative nodules, and loss of normal liver function-and may ultimately predispose to hepatocellular carcinoma (HCC).Importantly, regardless of the etiology, fibrosis across these settings is driven by activation of common cellular effector cells -hepatic stellate cells (HSCs).HSCs comprise approximately 10-15% of total liver cells and are mesenchymal in origin (2).Under physiological conditions, these cells remain in a quiescent state, playing essential roles in maintaining hepatic homeostasis.In response to liver injury, however, HSCs undergo activation and transition into a myofibroblast-like phenotype.This activated state is marked by enhanced proliferation, contractility, immune signaling capacity, and robust production of extracellular matrix (ECM).In HCC, HSCs are the primary source of cancer-associated fibroblasts (CAFs), which are key players in the reorganization of the tumor microenvironment (TME), and help to modulate cancer cell proliferation, migration, invasion and