{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE242nnn/GSE242111/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"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=GSE242111"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Local Delivery of SBRT and IL12 by mRNA Technology Overcomes Suppressive Barriers to Eliminate Pancreatic Cancer","description":"Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy carrying a five-year survival of about 10%. The immunosuppressive milieu in PDAC tumors has proven a significant hurdle to new and existing treatments, resulting in survival statistics that have barely changed in the last 5 decades. Here we present a novel combination treatment consisting of stereotactic body radiation therapy (SBRT) and IL-12 mRNA lipid nanoparticles delivered directly to the tumor of murine models of PDAC. This treatment was effective against primary and metastatic models of PDAC, leading to a dramatic reduction in tumor growth and even achieving cures in both settings. IL-12 protein concentrations were transient and remained localized primarily to the tumor. Depleting CD4 and CD8 T cells abrogated treatment efficacy, confirming these cells were the key players in the anti-tumor immune response generated. Subsequent single cell RNA sequencing from SBRT/IL-12 mRNA treated tumors demonstrated not only a complete loss of T cell exhaustion, but also an abundance of highly proliferative and effector T cell subtypes. SBRT was responsible for eliciting T cell receptor clonal expansion, whereas IL-12 licensed these cells with effector function, which was shown to be dependent on IFN.This is the first report of its kind demonstrating the utility of SBRT and IL-12 mRNA in PDAC.","dates":{"publication":"2026/08/29"},"accession":"GSE242111","cross_references":{"GSM":["GSM7749160","GSM7749161","GSM7749155","GSM7749154","GSM7749157","GSM7749156","GSM7749159","GSM7749158"],"GPL":["24247"],"GSE":["242111"],"taxon":["Mus musculus"]}}