Multiomics identifies tumor-intrinsic SREBP1 driving immune exclusion in hepatocellular carcinoma.

ABSTRACT: Immune checkpoint inhibitors (ICI) have improved patient outcomes in hepatocellular carcinoma (HCC); however, most patients do not experience durable benefit. The non-T cell-inflamed tumor microenvironment, characterized by limited CD8⁺ T-cell infiltration, reduced dendritic cell function, and low interferon-γ-associated gene expression, is associated with a lower likelihood of response to ICI. To nominate new therapeutic targets for overcoming ICI resistance in HCC, we conducted a large-scale multiomic analysis on 900+human specimens (RNA sequencing (RNA-seq), proteomics) and 31 tumor single-cell (sc) RNA-seq samples, with tissue validation through imaging mass cytometry (IMC) and spatial lipidomics by matrix-assisted laser desorption/ionization (MALDI), with experimental inves

SUBMITTER: Dadey RE 

PROVIDER: S-EPMC12314812 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature