{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336068/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336068"],"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 [ATAC-Seq]","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":"GSE336068","cross_references":{"GSM":["GSM9826504","GSM9826503","GSM9826506","GSM9826505","GSM9826510","GSM9826508","GSM9826507","GSM9826509"],"GPL":["34284"],"GSE":["336068"],"taxon":["Homo sapiens"]}}