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Activation of the stimulator of interferon genes pathway with an agonist such as 8803 can trigger anti-tumor immune responses. Using integrated molecular approaches, here we show that this pathway is targetable in both neoplastic and immune populations within the\u00a0meningioma\u00a0microenvironment. Meningioma tumor cells exhibit promoter hypomethylation and increased chromatin accessibility\u00a0of the STING genomic\u00a0locus,\u00a0associated with robust expression of this gene. Treatment of diverse patient meningiomas ex vivo with 8803 induces direct tumor cytotoxicity through inflammatory cell death pathways, including\u00a0induction of gasdermin D membrane pore formation. Release of necrotic tumor debris triggered by 8803 activates macrophages and upregulates matrix metalloproteinase production, facilitating degradation of extra-cellular collagen. Injection of preclinical meningiomas with 8803 induces survival benefits, including in an immunocompetent orthotopic setting, through remodeling of the tumor microenvironment, immune infiltration, and downregulation of tumor-mediated immune suppression, thereby nominating 8803 for treatment consideration in meningiomas.<\/jats:p>","DOI":"10.1038\/s41467-026-69296-1","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:46:31Z","timestamp":1770907591000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["STING activation induces cytotoxic and immune responses in meningiomas via inflammatory cell death pathways"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1044-8015","authenticated-orcid":false,"given":"Mark 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MAC holds the patent Cyclic dinucleotides as agonists of stimulator of interferon gene dependent signaling licensed to ImmunoGenesis, Inc. The remaining authors declare no potential competing interests related to the content of this manuscript.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2685"}}