Bibliographic Details
| Title: |
Myeloid activation clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer |
| Authors: |
Murphy, Brennah, Miyamoto, Taito, Manning, Bryan S., Mirji, Gauri, Ugolini, Alessio, Kannan, Toshitha, Hamada, Kohei, Zhu, Yanfang P., Claiborne, Daniel T., Huang, Lu, Zhang, Rugang, Nefedova, Yulia, Kossenkov, Andrew, Veglia, Filippo, Shinde, Rahul, Zhang, Nan |
| Source: |
The Journal of Experimental Medicine; December 2024, Vol. 221 Issue: 12 pe20231967-e20231967, 1p |
| Abstract: |
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 β-glucan and IFNγ (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. β-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. |
| Database: |
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