ACLY palmitoylation reprograms macrophages histone acetylation rewiring to repress hepatocellular carcinoma.

ACLY palmitoylation driven by palmitic acid enhances macrophage histone acetylation, suppressing hepatocellular carcinoma progression by reprogramming the tumor microenvironment.

• Why it matters: Understanding how macrophage metabolism influences chromatin accessibility and tumor suppression is critical for developing effective immunotherapies for hepatocellular carcinoma, yet the mechanisms remain unclear.
• What they did: The study examined the role of saturated fatty acids, especially palmitic acid, and ACLY palmitoylation in macrophages, using knockout models, dietary interventions, and in vivo macrophage reprogramming to explore their effects on tumor growth.
• The result: Findings demonstrate that ACLY palmitoylation stabilizes its activity, promoting histone acetylation of immune-related genes, which reprograms the tumor microenvironment and inhibits liver cancer, offering new immunotherapeutic strategies.