Myeloid cell networks determine reinstatement of original immune environments in recurrent ovarian cancer
Year: 2024
Type: preprint
Study design: Observational Study
Abstract: Summary Immunotherapy has produced disappointing results in recurrent ovarian cancer (OC). However, the prognostic value of tumour-infiltrating lymphocytes (TILs) is largely based on the analysis of treatment-naive tumours. To understand the immunobiology of recurrent cancers, and their evolution, we profiled 170 patient-matched primary-recurrent OC samples from 69 patients of two independent cohorts. By capturing heterogeneous TIL distributions, we identified four immune phenotypes associated with differential prognosis, TILs states and TILs:myeloid networks, which dictate malignant evolution after chemotherapy and recurrence. Notably, recurrent tumours recapitulate the immunogenic patterns of original cancers. Mirroring inflamed human OC, preclinical recurrent Brca1 mut tumours maintained activated TILs:dendritic cells (DCs) niches and immunostimulatory tumour-associated macrophages (TAMs). Conversely, recurrent Brca1 wt tumours displayed loss of TILs:DCs niches and accumulated immunosuppressive myeloid networks featuring Trem2/ApoE high TAMs and Nduf4l2 high / Galectin3 high malignant states. Our study highlights that persistent immunogenicity in recurrent OC is governed by the crosstalk between dissimilar myeloid cells and TILs, which is BRCA-dependent.
Authors: Eleonora Ghisoni, Fabrizio Benedetti, Aspram Minasyan, Paula Cunnea, Alizée J. Grimm, Noémie Fahr, Mathieu Desbuisson, Charlotte Capt, Nicolas Rayroux, Doga C. Gulhan, Julien Dagher, David Barras, Matteo Morotti, Juan A. Marín-Jiménez, Flavia De Carlo, Bovannak Stewen Chap, Giulia Spagnol, Mapi Fleury, Katerina Fortis, Julien Dorier, Stephanie Tissot, Sylvie Rusakiewicz, Humberto J. Ferreira, Michal Bassani-Stenberg, Elizabeth M. Swisher, Lana Kandalft, Spyridon A. Mastroyannis, Kathleen T. Montone, Daniel Powell, Mikaël J. Pittet, Janos L. Tanyi, George Coukos, Christina Fotopoulou, Jose R. Conejo-Garcia, Denarda Dangaj Laniti
Institutions: Centre Hospitalier Universitaire Vaudois, Ludwig Cancer Research, University of Lausanne, Imperial College London, Harvard University, Massachusetts General Hospital, Institut d'Investigació Biomédica de Bellvitge, University of Padua, University of Washington, University of Pennsylvania, University of Geneva, Duke University
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Defense, European Association for Cancer Research, Ludwig Institute for Cancer Research, Imperial Health Charity, National Institute for Health and Care Research, Imperial College London, Imperial College Healthcare NHS Trust, Centre Hospitalier Universitaire Vaudois, European Society for Medical Oncology
OpenAlex ID: W4396663985