{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE287nnn/GSE287799/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE287799"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Epigenetic modulation of polyamine biosynthetic pathways rectifies T cell dysfunction to enhance anti-tumor immunity in lung cancer [RNA-seq]","description":"T cell exhaustion (TEX) represents a critical target for immunotherapy in cancer. Nevertheless, T cells exhibit diminished responsiveness to immune checkpoint inhibitors once they transition to a terminally-exhausted state. Here, we employed an epigenetic drug screen and identified BET inhibitors (BETis) as enhancers of effector functions in primary exhausted T cells from malignant pleural effusions in lung cancer patients. Transcriptomics, metabolomics, and ATAC-seq analyses revealed that BETis reinvigorate TEX by activating the polyamine biosynthesis pathway, expanding intracellular polyamine pools, and altering chromatin accessibility. Genetic and pharmacological inhibition of ornithine decarboxylase (ODC), a key enzyme in this pathway, abolished BETi-mediated immunopotentiation. Single-cell RNA-seq demonstrated BETis reduced terminal TEX while promoting progenitor TEX through activation of the MYC-ODC axis. BETi treatment or adoptive transfer of BETi-treated T cells suppressed malignant pleural effusion formation in a syngeneic lung cancer model. These findings highlight an epigenetic-metabolic approach to enhance TEX plasticity and offers insights for novel cancer immunotherapies.","dates":{"publication":"2026/04/05"},"accession":"GSE287799","cross_references":{"GSM":["GSM8751553","GSM8751556","GSM8751557","GSM8751554","GSM8751555","GSM8751558"],"GPL":["24676"],"GSE":["287799"],"taxon":["Homo sapiens"]}}