Faculty, Staff and Student Publications

Publication Date

12-2-2024

Journal

Journal of Experimental Medicine

DOI

10.1084/jem.20231967

PMID

39570374

PMCID

PMC11586802

PubMedCentral® Posted Date

11-21-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Animals, Female, Ovarian Neoplasms, Ascites, Mice, Humans, Interferon-gamma, Cell Line, Tumor, Interleukins, Macrophages, Neoplasm Metastasis, Syk Kinase, Myeloid Cells, Mice, Inbred C57BL, Lectins, C-Type, Omentum

Published Open-Access

yes

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