{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306408/"]},"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=GSE306408"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"AntagomiRs targeting miR-146a and miR-21 induce tumor cell death and reinvigorate CD8+ T-cell function in large-cell transformed mycosis fungoides","description":"Large cell transformation in mycosis fungoides (LCT-MF) occurs in 20-50% of patients with advanced MF, the most common subtype of cutaneous T cell lymphoma (CTCL) and is associated with an aggressive clinical course and poor survival. We previously identified a distinct microRNA (miR) expression profile in LCT-MF with upregulation of miR-21 and miR-146a compared to non-LCT MF. Here, we investigated the efficacy of 2 novel synthesized and chemically modified antagomiRs amiR-146a, and amiR-21 linked to CpG–D19 for delivery on both tumor growth and T cell exhaustion. Targeting miR-146 and miR-21 alone or combined induced apoptosis through activated caspase 3/7 pathways and caused cell cycle arrest at the G2/M phase via the STAT3/CDK1/Cyclin B1 pathway in CTCL cell lines. In vivo, treatment reduced tumor growth and prolonged survival in mouse xenograft models. CD8+ T cells from LCT-MF patient biopsies exhibited upregulation of immune checkpoint proteins and activation of the STAT3/IRF4/BATF pathway, similar to exhausted CD8+ T cells from healthy donors stimulated to exhaustion in a CTCL culture model. Treatment of these exhausted CD8+ T cells with amiR-146a and amiR-21 alone or combined attenuated their exhaustion phenotype through decreased immune checkpoint expression, and enhanced cytokine production by inhibiting the STAT3/IRF4/BATF pathway. Collectively, our findings indicate that targeting miR-146a and miR-21 offers a promising new therapeutic approach for LCT-MF, by both suppressing tumor growth and restoring T cell function to enhance anti-tumor immunity.","dates":{"publication":"2026/08/23"},"accession":"GSE306408","cross_references":{"GSM":["GSM9198939","GSM9198928","GSM9198938","GSM9198937","GSM9198936","GSM9198935","GSM9198934","GSM9198933","GSM9198932","GSM9198931","GSM9198930","GSM9198929"],"GPL":["24676"],"GSE":["306408"],"taxon":["Homo sapiens"]}}