Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction

Gabriel Osborn, Jacobo López-Abente, Rebecca Adams, Roman Laddach, Melanie Grandits, Heather J. Bax, Jitesh Chauhan, Giulia Pellizzari, Mano Nakamura, Chara Stavraka, Alicia Chenoweth, Lais C. G. F. Palhares, Theodore Evan, Jessica Hui Cheah Lim, Amanda Gross, Lenny Moise, Shashi Jatiani, Mariangela Figini, Rodolfo Bianchini, Erika Jensen-Jarolim, Sharmistha Ghosh, Ana Montes, Ahmad Sayasneh, Rebecca Kristeleit, Sophia Tsoka, James Spicer, Debra H. Josephs and Sophia N. Karagiannis ()
Additional contact information
Gabriel Osborn: King’s College London, Guy’s Hospital
Jacobo López-Abente: King’s College London, Guy’s Hospital
Rebecca Adams: King’s College London, Guy’s Hospital
Roman Laddach: King’s College London, Guy’s Hospital
Melanie Grandits: King’s College London, Guy’s Hospital
Heather J. Bax: King’s College London, Guy’s Hospital
Jitesh Chauhan: King’s College London, Guy’s Hospital
Giulia Pellizzari: King’s College London, Guy’s Hospital
Mano Nakamura: King’s College London, Guy’s Hospital
Chara Stavraka: King’s College London, Guy’s Hospital
Alicia Chenoweth: King’s College London, Guy’s Hospital
Lais C. G. F. Palhares: King’s College London, Guy’s Hospital
Theodore Evan: King’s College London, Guy’s Hospital
Jessica Hui Cheah Lim: Guy’s and St Thomas’ NHS Foundation Trust
Amanda Gross: SeromYx Systems, Inc
Lenny Moise: SeromYx Systems, Inc
Shashi Jatiani: SeromYx Systems, Inc
Mariangela Figini: Istituto Nazionale dei Tumori
Rodolfo Bianchini: University of Vienna
Erika Jensen-Jarolim: University of Vienna
Sharmistha Ghosh: Guy’s and St Thomas’ NHS Foundation Trust
Ana Montes: Guy’s and St Thomas’ NHS Foundation Trust
Ahmad Sayasneh: Guy’s and St Thomas’ NHS Foundation Trust
Rebecca Kristeleit: Guy’s Hospital
Sophia Tsoka: Bush House
James Spicer: Guy’s Hospital
Debra H. Josephs: King’s College London, Guy’s Hospital
Sophia N. Karagiannis: King’s College London, Guy’s Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract 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-α, 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, FcεR-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.

Date: 2025
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DOI: 10.1038/s41467-025-57870-y

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