{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:39:33Z","timestamp":1792687173334,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01CA243555"],"award-info":[{"award-number":["R01CA243555"]}]},{"name":"National Cancer Institute","award":["R50CA274213"],"award-info":[{"award-number":["R50CA274213"]}]},{"name":"Intramural Research Program of the National Institutes of Health","award":["ZIABC012056"],"award-info":[{"award-number":["ZIABC012056"]}]},{"name":"National Cancer Institute","award":["T32CA128583"],"award-info":[{"award-number":["T32CA128583"]}]},{"name":"Osteosarcoma Institute","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"St. Baldrick's Foundation","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Battle Osteosarcoma","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Alex's Lemonade Stand Foundation for Childhood Cancer","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"MIB Agents","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Hyundai Hope On Wheels","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"CURE Childhood Cancer","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Enzo & Me Pediatric Cancer Foundation","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Rally Foundation","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>An immunosuppressive, macrophage-rich tumor microenvironment (TME) is a barrier to immunotherapy across many cancers including osteosarcoma, where immunotherapy has largely failed. cGAS-STING agonism has been explored to inflame such tumors, yet the mechanisms of STING-mediated TME remodeling remain poorly understood, especially in sarcomas. Using multi-modal single cell analysis, we show that systemic STING agonism in osteosarcoma triggers a myeloid-predominant inflammatory response and rapid tumor necrosis, followed by a T cell-mediated response, immunologic memory, and long-term cure in some models. Within two hours of treatment, STING agonism induces pro-inflammatory interferon programs in tumor-associated macrophages and monocytes, with additional contributions from endothelial cells. Efficacy persists in the absence of tumor-intrinsic STING or IFNAR, confirming that the therapeutic axis resides within the host TME rather than the tumor cell compartment. While cGAS-STING is frequently repressed in human osteosarcoma models of aggressive disease, a STING activation gene signature predicts survival in newly diagnosed patients, suggesting that this pathway is engaged during tumor progression. Together, these data identify an opportunity to exploit the myeloid compartment of osteosarcoma with STING pathway therapies, charting a path forward for engaging the TME to secure long term cure in an aggressive malignancy still treated with highly toxic chemotherapy.<\/jats:p>","DOI":"10.1172\/jci.insight.201731","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:41Z","timestamp":1792684841000},"source":"Crossref","is-referenced-by-count":0,"title":["STING agonism orchestrates myeloid-predominant tumor necrosis preceding T cell-dependent regression in osteosarcoma"],"prefix":"10.1172","author":[{"given":"Elizabeth P.","family":"Young","sequence":"first","affiliation":[{"name":"Division of Pediatric Oncology, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, UCSF, San 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