{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE332nnn/GSE332993/"]},"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=GSE332993"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Cobalt-mediated suppression of IFNγ-JAK-STAT1 signaling reprograms IDO1-driven immunosuppression for metalloimmunotherapy","description":"Metal ions are increasingly recognized as dynamic regulators of immune function, yet their systematic exploitation for cancer immunotherapy remains underexplored. Indoleamine 2,3-dioxygenase 1 (IDO1), an interferon-γ (IFNγ)-inducible immune checkpoint frequently upregulated in solid malignancies, catalyzes tryptophan degradation to kynurenine and establishes a metabolically immunosuppressive tumor microenvironment. Although IDO1 represents an attractive therapeutic target, strategies to modulate its activity with precision are limited. Here we identify cobalt ions (Co2+) as potent suppressors of IFNγ-induced IDO1 expression through a systematic screen of biologically relevant metal ions. Across multiple cancer cell lines, Co2+ markedly attenuated IDO1 expression and reduced kynurenine production. Mechanistically, Co2+ disrupted IFNγ-JAK-STAT1 signaling by engaging main receptor of IFNγ, IFNGR1, promoting its destabilization and degradation, thereby constraining tumor cell-intrinsic IDO1 induction, re-established kynurenine/tryptophan metabolic homeostasis and alleviating CD8+T cell exhaustion. These effects reprogrammed the immunosuppressive niche towards enhanced cytotoxic T cell function. To mitigate the off-target toxicity and immune cell damaging associated with free Co2+, we engineered ConaHA, a hyaluronic acid-based nanoparticle platform that enables sustained cobalt release and tumor-directed delivery. ConaHA potentiated cobalt-mediated immune checkpoint blockade while improving therapeutic tolerability in vivo, which dramatically improved the antitumor efficacy in subcutaneous Panc02, MC38 and B16F10 tumor models. Collectively, these findings uncover a previously unappreciated immunoregulatory function of Co2+ and establish a conceptual framework for metalloimmunotherapy through targeted modulation of metal-immune signaling axes.","dates":{"publication":"2026/09/23"},"accession":"GSE332993","cross_references":{"GSM":["GSM9756813","GSM9756814","GSM9756817","GSM9756818","GSM9756815","GSM9756816","GSM9756819","GSM9756820","GSM9756821"],"GPL":["24247"],"GSE":["332993"],"taxon":["Mus musculus"],"PMID":["[42758828]"]}}