Omics · study · 2026
Regulatory T cells Restrain CD4 T Cell Control of MHC-I-Deficient Metastatic Pancreatic Cancer Emerging After PD-L1 Blockade [EM-Seq]
Listed in NCBI GEO
We investigate mechanisms of immunotherapy resistance in pancreatic cancer.
Description
PD-L1 blockade selected for metastatic tumor variants with defective IFN-g–inducible MHC-I due to epigenetic Tap1 silencing. Restoration of MHC-I limited primary tumor growth but failed to prevent metastasis.
In contrast, regulatory T cell (TREG) depletion abrogated metastasis by unleashing conventional CD4 T cells. Metastasis was also mitigated by transfer of tumor-reactive CD4 T cells or by CTLA-4 blockade. Tumor-specific CD4 T cells adopt a TCF1⁺SLAMF6⁺ progenitor state in lymph nodes and further differentiate in malignant sites.
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CTLA4 blockade abrogated metastasis, drove intratumoral accumulation CD4 T cells with stemness and tissue residency features, producing a gene signature correlating with improved patient outcomes. MHC-I restoration with anti-CTLA4 prolonged animal survival. TREG and CD4 T cells co-localized in human tumors and abundance correlated with tumor MHC-I and overall survival.
Together, these findings identify actionable mechanisms of immune evasion and metastasis in immunotherapy-resistant cancer.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330323 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330323 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1463382 ncbi.nlm.nih.gov/bioproject/PRJNA1463382 ↗
project · from NCBI GEO
- PubMed 42361199 pubmed.ncbi.nlm.nih.gov/42361199 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Methylation 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 | GSE330323 | 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:methylation-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 |