Inhibition of ACLY enhances tumor immunogenicity and resolves MASH-driven HCC
Immunosuppressive tumor microenvironments are common in cancers such as metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma. To further investigate tumor–immune interactions, we performed spatial transcriptomics on livers from MASH-driven HCC mouse models (WD-DEN, WT or Acly KO mice and from WD-CCL4, Vehicle, or EVT0185 (100mg/kg) treated mice).  GO enrichment analysis of spatially resolved tumor cells showed increased fatty acid and lipid metabolism in both Acly KO and EVT0185-treated mice Spatial analysis also revealed a selective increase in B cells, but not T cells, macrophages, or NKT cells, in tumors from Acly KO and EVT0185-treated mice. Overall design: Two liver samples from WD-DEN HCC mouse models [WT (n=1) or Acly KO (n=1) mice] were used for spatial transcriptomic analysis. Two liver samples from WD-CCl4 HCC mouse models [Vehicle (n=1), or EVT0185 (100mg/kg) (n=1) treated mice] were used for spatial transcriptomic analysis.