{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330011/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"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=GSE330011"],"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 [scRNA-seq]","description":"We investigate mechanisms of immunotherapy resistance in pancreatic cancer. PD-L1 blockade selects for metastatic tumor variants with defective IFNγ-inducible MHC-I due to epigenetic silencing of Tap1. Restoring MHC-I limits primary tumor growth but fails to prevent metastasis. In contrast, regulatory T cell (TREG) depletion suppresses metastasis by unleashing CD4 T helper cells. Adoptive transfer of tumor-specific CD4 T cells impairs metastatic progression. Tumor-specific CD4 T cells in lymph nodes preferentially adopt a TCF1⁺SLAMF6⁺ precursor state. Intratumoral TREG targeting with anti–CTLA-4 abrogates metastasis, drives accumulation of stem-like, tissue-resident helper CD4 T cells, producing a gene signature associated with improved patient outcomes. Combined CTLA-4 blockade and MHC-I restoration eliminates metastasis and prolongs animal survival. In human tumors, TREG and CD4 helper T cells co-localize and correlate with both tumor MHC-I expression and overall survival. Together, these findings identify actionable mechanisms of immune evasion and metastasis in immunotherapy-resistant cancer.","dates":{"publication":"2026/06/26"},"accession":"GSE330011","cross_references":{"GSM":["GSM9715165","GSM9715166"],"GPL":["34328"],"GSE":["330011"],"taxon":["Mus musculus"]}}