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https://hdl.handle.net/2445/223347| Title: | Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer |
| Author: | Ghisoni, Eleonora Benedetti, Fabrizio Minasyan, Aspram Desbuisson, Mathieu Cunnea, Paula Grimm, Alizée J. Fahr, Noémie Capt, Charlotte Rayroux, Nicolas Carlo, Flavia de Gulhan, Doga C. Dagher, Julien Barras, David Morotti, Matteo Marín Jiménez, Juan A. Stewen Chap, Bovannak Santoro, Tania Spagnol, Giulia Fleury, Mapi Fortis, Katerina Dorier, Julien Townsend, Mary K. Tissot, Stephanie Rusakiewicz, Sylvie Ferreira, Humberto J. Kraemer, Anne I. Bassani Stenberg, Michal Swisher, Elizabeth M. Kandalaft, Lana A. Mastroyannis, Spyridon A. Montone, Kathleen T. Powell, Daniel J. Banerjee, Susana Terry, Kathryn L. Tworoger, Shelley S. Pittet, Mikaël J. Tanyi, Janos L. Coukos, George Merritt, Melissa A. Fotopoulou, Christina Conejo García, José R. Dangaj Laniti, Denarda |
| Keywords: | Càncer d'ovari Sistema immunitari Ovarian cancer Immune system |
| Issue Date: | 31-Jul-2025 |
| Publisher: | Elsevier BV |
| Abstract: | Immunotherapy has shown limited success in recurrent ovarian cancer (OC), with prognostic insights largely derived from treatment-naive tumors. We analyzed 697 tumor samples (566 primary and 131 recurrent) from 595 OC patients across five independent cohorts, capturing tumor-infiltrating lymphocytes (TILs) heterogeneity and identifying four immune phenotypes linked to prognosis and TIL:myeloid networks driving malignant progression. We found that in preclinical mouse models, mirroring inflamed human OCs, the recurrent Brca1mut tumors maintained activated TILs:dendritic cells (DCs) niches but evaded immune control through upregulation of COX/PGE2 signaling. Conversely, recurrent Brca1wt tumors displayed loss of TILs:DCs niches and accumulated immunosuppressive tumor microenvironment (TME) networks featuring Trem2/ ApoEhigh tumor associated macrophages (TAMs) and Nduf4l2high/Galectin3high malignant states. Recurrent tumors recapitulate the immunogenic landscapes of original cancers. Our findings reveal BRCA-dependent TIL:myeloid crosstalk as key to persistent immunogenicity in recurrent OC and propose new targets to enhance chemotherapy efficacy. |
| Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.ccell.2025.07.005 |
| It is part of: | Cancer Cell, 2025, vol. 43, num. 8, p. 1568-1586 |
| URI: | https://hdl.handle.net/2445/223347 |
| Related resource: | https://doi.org/10.1016/j.ccell.2025.07.005 |
| ISSN: | 1878-3686 |
| Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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|---|---|---|---|---|
| PIIS1535610825002764.pdf | 10.41 MB | Adobe PDF | View/Open |
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