https://phaidra.vetmeduni.ac.at/o:4122 Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction Osborn, Gabriel Gabriel Osborn López-Abente, Jacobo Jacobo López-Abente Adams, Rebecca Rebecca Adams Laddach, Roman Roman Laddach Grandits, Melanie Melanie Grandits Bax, Heather J. Heather J. Bax 0000-0003-0432-4160 Chauhan, Jitesh Jitesh Chauhan Pellizzari, Giulia Giulia Pellizzari 0000-0003-0387-1912 Nakamura, Mano Mano Nakamura Stavraka, Chara Chara Stavraka 0000-0001-7623-299X Chenoweth, Alicia Alicia Chenoweth Palhares, Lais C. G. F. Lais C. G. F. Palhares Evan, Theodore Theodore Evan Lim, Jessica Hui Cheah Jessica Hui Cheah Lim Gross, Amanda Amanda Gross Moise, Lenny Lenny Moise 0000-0002-4410-865X Jatiani, Shashi Shashi Jatiani 0000-0003-0724-6583 Figini, Mariangela Mariangela Figini 0000-0001-9001-8754 Bianchini, Rodolfo Rodolfo Bianchini 0000-0003-0351-6937 Jensen-Jarolim, Erika Erika Jensen-Jarolim 0000-0003-4019-5765 University of Veterinary Medicine Vienna Ghosh, Sharmistha Sharmistha Ghosh Montes, Ana Ana Montes Sayasneh, Ahmad Ahmad Sayasneh Kristeleit, Rebecca Rebecca Kristeleit 0000-0003-3825-1326 Tsoka, Sophia Sophia Tsoka Spicer, James James Spicer 0000-0003-3732-8491 Josephs, Debra H. Debra H. Josephs Karagiannis, Sophia N. Sophia N. Karagiannis 0000-0002-4100-7810 Nature Portfolio journal article open access eng Ovarian cancer is the most lethal gynaecological cancer and treatment options remain limited. 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. Humans Female Ovarian Neoplasms Immunology Ovarian Neoplasms Drug Therapy Ovarian Neoplasms Pathology T-Lymphocytes, Regulatory Immunology T-Lymphocytes, Regulatory Drug Effects Macrophages Immunology Macrophages Drug Effects Immunoglobulin E Immunology Carcinoma, Ovarian Epithelial Immunology Carcinoma, Ovarian Epithelial Drug Therapy Receptors, IgE Metabolism Folate Receptor 1 Immunology Inflammation Immunology Middle Aged CD8-Positive T-Lymphocytes Immunology http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:4122/download 10.1038/s41467-025-57870-y https://phaidra.vetmeduni.ac.at/o:605 application/pdf Nature Communications issn:2041-1723 VoR Nature Communications 16 1 7.63 MB 2025