{"database":"GEO","file_versions":[],"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=GSE328028"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"T cell lymphoma associated STAT3 variants impose a type 1 regulatory phenotype","description":"STAT3 signaling is fundamental to T cells, where it underlies basic cellular processes like metabolism and apoptosis, and specialized processes like differentiation and cytokine production. However, mutations of STAT3 are strikingly prevalent in T cell cancers and aberrant or excessive STAT3 signaling is thought to mobilize cellular pathways that encourage malignancy. To better understand how STAT3 mutations drive T cell cancers, we compared two frequent cancer-associated variants, Y640F and N647I, at cellular and molecular levels. Using a retrogenic system, we demonstrate that they are qualitatively similar yet quantitatively distinct; each bears a gain-of-function phenotype but Y640F has greater transcriptome-wide effects. We also discovered that these and other common STAT3 mutants invoke a T regulatory 1 (Tr1) gene program characterized by expression of IL-10 and other factors that dampen T cell responses, most notably LAG3 and CD39. Importantly, Tr1 ’skewing’ is evident in both mouse T cells expressing cancer-associated STAT3 variants and humans afflicted with T cell malignancies. These studies advance current understanding of how cancer-associated mutations impact STAT3 function and reveal anti-inflammatory properties that may help transformed T cells persist, expand and/or avoid eradication.","dates":{"publication":"2026/04/14"},"accession":"GSE328028","cross_references":{"GSM":["GSM9670569","GSM9670568","GSM9670578","GSM9670577","GSM9670576","GSM9670575","GSM9670574","GSM9670573","GSM9670572","GSM9670571","GSM9670570","GSM9670579","GSM9670567","GSM9670566","GSM9670587","GSM9670565","GSM9670564","GSM9670586","GSM9670585","GSM9670563","GSM9670584","GSM9670562","GSM9670561","GSM9670583","GSM9670582","GSM9670560","GSM9670581","GSM9670580"],"GPL":["13112"],"GSE":["328028"],"taxon":["Mus musculus"]}}