Omics · study · 2026
Anti-PD-1 Treatment in an HFD/CCl4-Accelerated MASH-Fibrosis Mouse Model
Listed in NCBI GEO
Immune checkpoint inhibitors (ICIs) show variable efficacy in hepatocellular carcinoma (HCC) depending on etiology.
Description
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.
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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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE331nnn/GSE331440 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331440 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1468132 ncbi.nlm.nih.gov/bioproject/PRJNA1468132 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE331440 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |