Higher basal tumor immune activity coupled with a systemic immune response improves liver cancer outcomes

This study examines how systemic immune responses and liver immune activity influence liver tumor development. In a diethylnitrosamine (DEN)‑induced mouse model of hepatocellular carcinoma, mice were fed different diets for 26 weeks to assess the impact of metabolic and inflammatory conditions on tumor progression. Tumor burden varied across diets, with increased tumor formation in some diets and a diet with combined cholesterol and cholic acid showing tumor burdens similar to controls. Flow cytometry revealed that mice on the combined diet exhibited the strongest expansion and activation of bone marrow hematopoietic stem and progenitor cells (HSPCs). RNA‑seq was performed on tumor and non‑tumor liver tissues to profile diet‑associated transcriptional changes, and weighted gene co‑expression network analysis (WGCNA) identified conserved immune‑related gene expression modules. Enhanced systemic hematopoietic responses were associated with stronger liver immune gene expression and increased innate immune cell infiltration, correlating with reduced tumor burden. These findings highlight a link between systemic hematopoietic activation, hepatic immune responses, and liver tumor outcomes.