ACLY inhibition promotes tumour immunity and suppresses liver cancer.

ABSTRACT: Immunosuppressive tumour microenvironments are common in cancers such as metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC) (MASH-HCC)^1-3. Although immune cell metabolism influences effector function, the effect of tumour metabolism on immunogenicity is less understood⁴. ATP citrate lyase (ACLY) links substrate availability and mitochondrial metabolism with lipid biosynthesis and gene regulation^5-7. Although ACLY inhibition shows antiproliferative effects in various tumours, clinical translation has been limited by challenges in inhibitor development and compensatory metabolic pathways^8-12. Here, using a mouse model of MASH-HCC that mirrors human disease, genetic inhibition of ACLY in hepatocytes and tum

SUBMITTER: Gautam J 

PROVIDER: S-EPMC12422966 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature