{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331440"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Anti-PD-1 Treatment in an HFD/CCl4-Accelerated MASH-Fibrosis Mouse Model","description":"Immune checkpoint inhibitors (ICIs) show variable efficacy in hepatocellular carcinoma (HCC) depending on etiology. In metabolic dysfunction-associated steatohepatitis (MASH), PD-1+ CD8+ T cells may paradoxically drive liver injury. We investigated whether PD-1 blockade exacerbates liver fibrosis in a non-neoplastic MASH environment. Male C57BL/6J mice were fed a high-fat diet (HFD) for 18 weeks, with weekly carbon tetrachloride (CCl4) during the final 12 weeks. Mice received anti-PD-1 antibody or isotype control every 3 days during the HFD/CCl4 phase. Liver injury, immune cell accumulation, and fibrosis were evaluated via biochemistry, histology, flow cytometry, and transcriptomic analysis. The HFD/CCl4 model exhibited significant hepatic accumulation of PD-1+ CD8+ T cells. PD-1 blockade increased AST/ALT and LDH levels, alongside heightened necroinflammation. Transcriptomic analysis showed upregulation of exhaustion-associated and cytotoxicity-related genes. Histologically, anti-PD-1 treatment was associated with periportal accumulation of F4/80+ macrophages and increased collagen deposition. Notably, we observed close spatial proximity between F4/80+ macrophages and α-smooth muscle actin+ myofibroblasts, suggesting a pro-fibrotic immune-stromal axis. PD-1 inhibition aggravates liver injury and accelerates fibrosis in this MASH model. These findings suggest that PD-1 blockade may provoke unintended pathological consequences in the context of chronic metabolic liver injury.","dates":{"publication":"2026/06/02"},"accession":"GSE331440","cross_references":{"GSM":["GSM9745921","GSM9745922","GSM9745923","GSM9745924","GSM9745920","GSM9745919"],"GPL":["34871"],"GSE":["331440"],"taxon":["Mus musculus"]}}