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In a recent first-in-class Phase I trial, the monoclonal IgE antibody MOv18, specific for the tumour-associated antigen Folate Receptor-?, was well-tolerated and preliminary anti-tumoural activity observed. Pre-clinical studies identified macrophages as mediators of tumour restriction and pro-inflammatory activation by IgE. However, the mechanisms of IgE-mediated modulation of macrophages and downstream tumour immunity in human cancer remain unclear. Here we study macrophages from patients with epithelial ovarian cancers naive to IgE therapy. High-dimensional flow cytometry and RNA-seq demonstrate immunosuppressive, Fc?R-expressing macrophage phenotypes. Ex vivo co-cultures and RNA-seq interaction analyses reveal immunosuppressive associations between patient-derived macrophages and regulatory T (Treg) cells. MOv18 IgE-engaged patient-derived macrophages undergo pro-inflammatory repolarisation ex vivo and display induction of a hyperinflammatory, T cell-stimulatory subset. IgE reverses macrophage-promoted Treg cell induction to increase CD8+ T cell expansion, a signature associated with improved patient prognosis. On-treatment tumours from the MOv18 IgE Phase I trial show evidence of this IgE-driven immune signature, with increased CD68+ and CD3+ cell infiltration. We demonstrate that IgE induces hyperinflammatory repolarised states of patient-derived macrophages to inhibit Treg cell immunosuppression. These processes may collectively promote immune activation in ovarian cancer patients receiving IgE therapy."}]}],"bf:provisionActivity":[{"@type":"bf:Publication","bf:agent":[{"@type":"schema:Organization","schema:name":[{"@value":"Nature Portfolio"}]}]}],"dce:rights":[{"@language":"eng","@value":"© 2025. The Author(s)"}],"dce:subject":[{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"Humans"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"Female"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"Ovarian Neoplasms Immunology"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"Ovarian Neoplasms Drug Therapy"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"Ovarian Neoplasms Pathology"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"T-Lymphocytes, Regulatory Immunology"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"T-Lymphocytes, Regulatory Drug Effects"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"Macrophages Immunology"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"Macrophages Drug 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