{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330482/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Mus musculus"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330482"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Regulatory T cells Restrain CD4 T Cell Control of MHC-I-Deficient Metastatic Pancreatic Cancer Emerging After PD-L1 Blockade [ATAC-seq]","description":"We investigate mechanisms of immunotherapy resistance in pancreatic cancer. 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. 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.","dates":{"publication":"2026/06/26"},"accession":"GSE330482","cross_references":{"GSM":["GSM9727620","GSM9727616","GSM9727615","GSM9727618","GSM9727617","GSM9727619"],"GPL":["34475"],"GSE":["330482"],"taxon":["Mus musculus"]}}