View in EDS

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

Saved in:
Bibliographic Details
Title: Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction
Authors: Osborn, Gabriel, López-Abente, Jacobo, Adams, Rebecca, Laddach, Roman, Grandits, Melanie, Bax, Heather J., Chauhan, Jitesh, Pellizzari, Giulia, Nakamura, Mano, Stavraka, Chara, Chenoweth, Alicia, Palhares, Lais C. G. F., Evan, Theodore, Lim, Jessica Hui Cheah, Gross, Amanda, Moise, Lenny, Jatiani, Shashi, Figini, Mariangela, Bianchini, Rodolfo, Jensen-Jarolim, Erika, Ghosh, Sharmistha, Montes, Ana, Sayasneh, Ahmad, Kristeleit, Rebecca, Tsoka, Sophia, Spicer, James, Josephs, Debra H., Karagiannis, Sophia N.
Source: Nat Commun
Nature Communications, Vol 16, Iss 1, Pp 1-20 (2025)
Osborn, G, López-Abente, J, Adams, R, Laddach, R, Grandits, M, Bax, H J, Chauhan, J, Pellizzari, G, Nakamura, M, Stavraka, C, Chenoweth, A, Palhares, L C G F, Evan, T, Lim, J H C, Gross, A, Moise, L, Jatiani, S, Figini, M, Bianchini, R, Jensen-Jarolim, E, Ghosh, S, Montes, A, Sayasneh, A, Kristeleit, R, Tsoka, S, Spicer, J, Josephs, D H & Karagiannis, S N 2025, ' Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction ', Nature Communications, vol. 16, no. 1, 2903 . https://doi.org/10.1038/s41467-025-57870-y, https://doi.org/10.1038/s41467-025-57870-y
Publisher Information: Springer Science and Business Media LLC, 2025.
Publication Year: 2025
Subject Terms: Receptors, IgE/metabolism, Science, Carcinoma, Ovarian Epithelial Drug Therapy, Ovarian Neoplasms Pathology, T-Lymphocytes, Regulatory/immunology, Macrophages/immunology, Carcinoma, Ovarian Epithelial, CD8-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes/immunology, T-Lymphocytes, Regulatory, Article, Carcinoma, Ovarian Epithelial Immunology, CD8-Positive T-Lymphocytes Immunology, Folate Receptor 1/immunology, Inflammation Immunology, Carcinoma, Ovarian Epithelial/immunology, Macrophages Drug Effects, Folate Receptor 1 Immunology, Humans, Folate Receptor 1, Ovarian Neoplasms Drug Therapy, Ovarian Neoplasms, Inflammation, Receptors, IgE, Macrophages, Receptors, IgE Metabolism, T-Lymphocytes, Regulatory Immunology, Macrophages Immunology, Inflammation/immunology, Immunoglobulin E, Middle Aged, Ovarian Neoplasms Immunology, Immunoglobulin E Immunology, Ovarian Neoplasms/immunology, Immunoglobulin E/immunology, Female, T-Lymphocytes, Regulatory Drug Effects
Description: 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.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 2041-1723
DOI: 10.1038/s41467-025-57870-y
Access URL: https://pubmed.ncbi.nlm.nih.gov/40210642
https://doaj.org/article/26e18d7bcf7042dbbc220559f04677f5
https://kclpure.kcl.ac.uk/portal/en/publications/1797ddd9-2f9f-4b88-be79-aea7103f71af
Rights: CC BY
Accession Number: edsair.doi.dedup.....bda42604a8efc5d8dc90aec7047ea2be
Database: OpenAIRE
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.
ISSN:20411723
DOI:10.1038/s41467-025-57870-y