| First Author | Murphy B | Year | 2024 |
| Journal | J Exp Med | Volume | 221 |
| Issue | 12 | PubMed ID | 39570374 |
| Mgi Jnum | J:360138 | Mgi Id | MGI:7797663 |
| Doi | 10.1084/jem.20231967 | Citation | Murphy B, et al. (2024) Myeloid activation clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer. J Exp Med 221(12) |
| abstractText | Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of <30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of beta-glucan and IFNgamma (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. beta-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent 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. |
