{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE303nnn/GSE303456/"]},"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=GSE303456"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Sequential Imatinib and Anti-PD-1 Therapy in KIT-Altered Melanoma: Mechanistic Insights and Clinical Benefit","description":"KIT is a key oncogenic driver in triple-wildtype melanoma and represents a rational therapeutic target for KIT inhibitors such as imatinib. However, the tumor immune microenvironment in KIT-altered melanoma and optimal strategies to integrate immunotherapy remain poorly defined. In this study, we found that melanomas harboring KIT mutations or amplifications exhibited reduced CD8⁺ T cell infiltration, indicative of an immune-cold phenotype. Imatinib treatment reversed this Immunosuppressive microenvironment by enhancing CD8⁺ T cell infiltration and cytotoxic activity. Furthermore, imatinib upregulated O-GlcNAc transferase (OGT), which functions as a protein lactyltransferase and increased PD-L1 expression through lysine lactylation, thereby sensitizing tumors to anti–PD-1 therapy. Based on these findings, we conducted an open-label, single-arm phase II clinical trial in patients with advanced or metastatic KIT-altered melanoma. Patients received imatinib monotherapy as induction for six weeks, followed by combination therapy with toripalimab, an anti–PD-1 antibody. The combiniation therapy was well-tolerated and demonstrated encouraging clinical activity, with an objective response rate (ORR) of 59.4% in the overall cohort, 73.9% in patients with exon 11/13 mutations, and 100% in those with exon 11 mutation plus amplification—markedly higher than the ORRs of 23.3% with imatinib monotherapy and 25.7% with anti–PD-1 monotherapy. Median progression-free survival and overall survival were 8.2 months (95% CI, 6.5–9.9) and 15.1 months (95% CI, 13.1–20.8), respectively. These results support the use of imatinib as an immune-sensitizing induction therapy prior to PD-1 blockade in KIT-altered melanoma and highlight the therapeutic relevance of OGT-mediated PD-L1 regulation.","dates":{"publication":"2026/07/23"},"accession":"GSE303456","cross_references":{"GSM":["GSM9127092","GSM9127091","GSM9127090","GSM9127096","GSM9127095","GSM9127094","GSM9127093","GSM9127133","GSM9127111","GSM9127099","GSM9127110","GSM9127132","GSM9127131","GSM9127098","GSM9127130","GSM9127097","GSM9127137","GSM9127115","GSM9127136","GSM9127114","GSM9127113","GSM9127135","GSM9127134","GSM9127112","GSM9127119","GSM9127118","GSM9127117","GSM9127116","GSM9127122","GSM9127100","GSM9127121","GSM9127120","GSM9127126","GSM9127104","GSM9127125","GSM9127103","GSM9127102","GSM9127124","GSM9127123","GSM9127101","GSM9127108","GSM9127107","GSM9127129","GSM9127128","GSM9127106","GSM9127127","GSM9127105","GSM9127109"],"GPL":["34284"],"GSE":["303456"],"taxon":["Homo sapiens"]}}