Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction
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...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57870-y |
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| author | 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 Sophia N. Karagiannis |
| author_facet | 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 Sophia N. Karagiannis |
| author_sort | Gabriel Osborn |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-26e18d7bcf7042dbbc220559f04677f5 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-26e18d7bcf7042dbbc220559f04677f52025-08-20T02:17:05ZengNature PortfolioNature Communications2041-17232025-04-0116112010.1038/s41467-025-57870-yHyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interactionGabriel Osborn0Jacobo López-Abente1Rebecca Adams2Roman Laddach3Melanie Grandits4Heather J. Bax5Jitesh Chauhan6Giulia Pellizzari7Mano Nakamura8Chara Stavraka9Alicia Chenoweth10Lais C. G. F. Palhares11Theodore Evan12Jessica Hui Cheah Lim13Amanda Gross14Lenny Moise15Shashi Jatiani16Mariangela Figini17Rodolfo Bianchini18Erika Jensen-Jarolim19Sharmistha Ghosh20Ana Montes21Ahmad Sayasneh22Rebecca Kristeleit23Sophia Tsoka24James Spicer25Debra H. Josephs26Sophia N. Karagiannis27St. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalCancer Centre at Guy’s, Guy’s and St Thomas’ NHS Foundation TrustSeromYx Systems, IncSeromYx Systems, IncSeromYx Systems, IncANP2, Department of Advanced Diagnostics, Fondazione IRCCS, Istituto Nazionale dei TumoriComparative Medicine, The Interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University of Vienna, University of ViennaComparative Medicine, The Interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University of Vienna, University of ViennaCancer Centre at Guy’s, Guy’s and St Thomas’ NHS Foundation TrustCancer Centre at Guy’s, Guy’s and St Thomas’ NHS Foundation TrustCancer Centre at Guy’s, Guy’s and St Thomas’ NHS Foundation TrustSchool of Cancer & Pharmaceutical Sciences, King’s College London, Guy’s HospitalDepartment of Informatics, Faculty of Natural, Mathematical and Engineering Sciences, King’s College London, Bush HouseSchool of Cancer & Pharmaceutical Sciences, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, King’s College London, Guy’s HospitalAbstract 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.https://doi.org/10.1038/s41467-025-57870-y |
| spellingShingle | 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 Sophia N. Karagiannis Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction Nature Communications |
| title | Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction |
| title_full | Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction |
| title_fullStr | Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction |
| title_full_unstemmed | Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction |
| title_short | Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction |
| title_sort | hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti tumour ige antibody mov18 restricts an immunosuppressive macrophage treg cell interaction |
| url | https://doi.org/10.1038/s41467-025-57870-y |
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