{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318203/"]},"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=GSE318203"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"NR2F6 Functions as a Key Transcriptional Checkpoint Enforcing Dysfunction of Human CD3+ T cells and Limiting CAR-T Cell Potency","description":"Although NR2F6 regulates lymphocyte activation in murine models, its function in human T cells remains incompletely defined. Here, we identify NR2F6 as a TCR inducible transcriptional checkpoint that limits effector potency in human CD3⁺ T cells, including chimeric antigen receptor (CAR) T cells. In an anti EGFR CAR T cell-A549 co culture model, enforced NR2F6 expression, mimicking its upregulation in tumor infiltrating lymphocytes, markedly impairs killing under repeated tumor challenge. In polyclonal T cells, NR2F6 overexpression and CRISPR/Cas9-mediated ablation produced directionally opposing effects, supporting its role as a negative regulator of activation, differentiation-associated programs, and cytokine production. Mechanistically, transcriptomic, epigenomic, and nuclear protein analyses are consistent with suppression of NFAT , AP 1 , and NF κB-associated pathways and reveal context dependent changes in TCF 1-associated readouts. Collectively, these findings position NR2F6 as a signaling integrated transcriptional checkpoint that contributes to dysfunctional T cell states and may promote tumor immune evasion in humans.","dates":{"publication":"2026/09/09"},"accession":"GSE318203","cross_references":{"GSM":["GSM9489213","GSM9489202","GSM9489212","GSM9489201","GSM9489211","GSM9489200","GSM9489210","GSM9489199","GSM9489198","GSM9489197","GSM9489209","GSM9489219","GSM9489208","GSM9489207","GSM9489218","GSM9489206","GSM9489217","GSM9489216","GSM9489205","GSM9489215","GSM9489204","GSM9489203","GSM9489214"],"GPL":["34284"],"GSE":["318203"],"taxon":["Homo sapiens"]}}