{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334585/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"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=GSE334585"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"iNOS is a key mediator of anti-PD-1 melanoma therapy response","description":"Background: Inducible nitric oxide synthase (iNOS) and its product nitric oxide (NO) were historically linked to poor melanoma outcomes, yet recent evidence shows NO supports anti-tumor immunity. This study examines how iNOS shapes anti–PD-1 efficacy, particularly through interferon signaling. Methods: B16 D5 melanoma tumors were implanted in wild-type (WT) and iNOS knockout (KO) mice to compare tumor growth and response to anti–PD-1 therapy. Flow cytometry, apoptosis assays, and RNA sequencing assessed NO production, PD-L1 expression, and interferon-related gene activation. In vitro, melanoma cells were treated with NO donors (DETA NONOate, SNAP) to assess proliferation and apoptosis. Peripheral blood mononuclear cells from 27 melanoma patients receiving anti–PD-1 therapy were analyzed with multiparameter flow cytometry to correlate NO-associated immune subsets with progression-free survival (PFS). Results: Tumors grew significantly faster in iNOS KO mice, and anti–PD-1 therapy had no effect, demonstrating that iNOS-derived NO contributes to treatment efficacy. NO donors inhibited melanoma proliferation and induced apoptosis in vitro. Transcriptomic analysis showed anti–PD 1 upregulated interferon pathway genes (STAT1, IRF1, IFNB1) in WT but not iNOS KO mice. In patients, a NO-producing dendritic cell subset (DAF FM⁺CD11c⁺) was associated with improved PFS (hazard ratio 0.453; 95% CI=0.270-0.992; p = 0.048), indicating a NO-dependent enhancement of interferon-driven immune activity.","dates":{"publication":"2026/07/15"},"accession":"GSE334585","cross_references":{"GSM":["GSM9791337","GSM9791315","GSM9791316","GSM9791338","GSM9791339","GSM9791317","GSM9791318","GSM9791319","GSM9791340","GSM9791341","GSM9791342","GSM9791320","GSM9791343","GSM9791321","GSM9791322","GSM9791344","GSM9791345","GSM9791323","GSM9791324","GSM9791346","GSM9791325","GSM9791347","GSM9791348","GSM9791326","GSM9791349","GSM9791327","GSM9791328","GSM9791306","GSM9791329","GSM9791307","GSM9791308","GSM9791309","GSM9791350","GSM9791351","GSM9791330","GSM9791352","GSM9791353","GSM9791331","GSM9791310","GSM9791332","GSM9791333","GSM9791311","GSM9791334","GSM9791312","GSM9791313","GSM9791335","GSM9791336","GSM9791314"],"GPL":["24247"],"GSE":["334585"],"taxon":["Mus musculus"],"PMID":["[42440610]"]}}