GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328028/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328028GEOGSEfalseT cell lymphoma associated STAT3 variants impose a type 1 regulatory phenotypeSTAT3 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.2026/04/14GSE328028GSM9670569GSM9670568GSM9670578GSM9670577GSM9670576GSM9670575GSM9670574GSM9670573GSM9670572GSM9670571GSM9670570GSM9670579GSM9670567GSM9670566GSM9670587GSM9670565GSM9670564GSM9670586GSM9670585GSM9670563GSM9670584GSM9670562GSM9670561GSM9670583GSM9670582GSM9670560GSM9670581GSM967058013112328028Mus musculus