News Summary

• Fibroinflammatory liver microenvironment (FILM) is prevalent in hepatocellular carcinoma (HCC) FILM suppresses gasdermin E (GSDME)-dependent pyroptosis and promotes immune suppression and anti-PD-1 resistance.
• PPARα downregulation reduces pyruvate dehydrogenase kinase 4 (PDK4) expression, mitochondrial reactive oxygen species production, caspase-3 activation and GSDME cleavage.
• Conversely, ligand activation of tumor intrinsic PPAR α restores the PDK4–ROS–caspases-3–G SDME axis.