Omics · study · 2026
IL1R1 blockade augments CD40 agonist mediated immunity in pancreatic cancer
Listed in NCBI GEO
Pancreatic ductal adenocarcinoma (PDAC) has a poor survival rate and limited treatments.
Description
Agonistic CD40 antibodies are promising, but clinical trials have shown only modest efficacy and significant hepatotoxicity. We previously reported that IL-1 pathway blockade enhances CD40 agonist efficacy against melanoma by depleting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs; CD11b+Ly6C+Ly6G+).
Because PMN-MDSCs also cause liver toxicity, we investigated the impact of IL-1R1 blockade on the efficacy and toxicity of agonistic CD40 antibody therapy in PDAC. Agonistic CD40 antibody therapy induced immune activation and significantly prolonged survival in orthotopic PDAC-bearing mice. The combination of an agonistic CD40 antibody and IL-1R1 blockade upregulated multiple immune-related pathways and enhanced innate and adaptive responses.
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However, it did not further improve CD40 efficacy or reduce liver toxicity. The efficacy of the CD40 agonist was partially dependent on CD8⁺ T cells. Our findings underscore the complex role of IL-1 signaling in modulating immune responses in PDAC and caution against pursuing IL-1R1 blockade, either as monotherapy or combined with agonistic CD40 antibodies, in clinical trials for PDAC.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE331nnn/GSE331215 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331215 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1467185 ncbi.nlm.nih.gov/bioproject/PRJNA1467185 ↗
project · from NCBI GEO
- PubMed 41935073 pubmed.ncbi.nlm.nih.gov/41935073 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE331215 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |