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Here, we report that intraperitoneal administration of \u03b2-glucan and IFN\u03b3 (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. \u03b2-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk\u2013dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacy in vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.<\/jats:p>","DOI":"10.1084\/jem.20231967","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T02:20:50Z","timestamp":1729045250000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Myeloid activation clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer"],"prefix":"10.1084","volume":"221","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-6513","authenticated-orcid":true,"given":"Brennah","family":"Murphy","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04wncat98","id-type":"ROR","asserted-by":"publisher"}],"name":"Immunology, Microenvironment and Metastasis Program, Ellen and Ronald Caplan Cancer Center, The Wistar Institute 1 , Philadelphia, 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