{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE279nnn/GSE279355/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"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=GSE279355"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Epigenetic plus cytokine therapy evades checkpoint blockade resistance by potentiating cytotoxic CD8+ T cells with stem-immunity clusters [ATAC-seq]","description":"Checkpoint blockade (CPB) has limited efficacy in patients with colorectal carcinoma (CRC), warranting improved therapeutic approaches. Here, we find the combination of anti-PD-1, the class I histone deacetylase inhibitor entinostat, and the IL-15 superagonist N-803 elicited anti-tumor immunity and increased survival in a murine CPB-resistant CRC and in other tumor types with varying antigen presentation deficiencies. Triple therapy increased CRC tumor and draining lymph node stem-like TCF1+CD8+ T cells, and tumor granzyme B+ CD8+ T and NK cells. Increased stem-immunity clusters comprising TCF1+CD8+ T cells, cDC1, and B cells were observed in tumors with concerted cytokine and chemokine production. Triple therapy also augmented cytotoxicity of patient-derived PBMCs in vitro. Moreover, we identified a biomarker signature of triple therapy‒induced stem-immunity clusters that was associated favorable clinical response across multiple cancers, including CPB-experienced. Thus entinostat, N-803 and anti-PD-1 serve as a promising combinatorial approach for CRC patients, including those refractory to CPB.","dates":{"publication":"2026/08/31"},"accession":"GSE279355","cross_references":{"GSM":["GSM8567929","GSM8567928","GSM8567939","GSM8567919","GSM8567921","GSM8567932","GSM8567931","GSM8567942","GSM8567920","GSM8567934","GSM8567923","GSM8567922","GSM8567933","GSM8567925","GSM8567936","GSM8567924","GSM8567935","GSM8567938","GSM8567927","GSM8567926","GSM8567937","GSM8567941","GSM8567930","GSM8567940"],"GPL":["24247"],"GSE":["279355"],"taxon":["Mus musculus"]}}