Myeloid cell networks determine reinstatement of original immune environments in recurrent ovarian cancer

Eleonora Ghisoni; Fabrizio Benedetti; Aspram Minasyan; Mathieu Desbuisson; Paula Cunnea; Alizée J Grimm; Noémie Fahr; Charlotte Capt; Nicolas Rayroux; Flavia De Carlo; D. C. Gulhan; Julien Dagher; David Barras; Matteo Morotti; Juan A. Marín‐Jiménez; Bovannak Stewen Chap; Tania Santoro; Giulia Spagnol; Mapi Fleury; Katerina Fortis; Julien Dorier; Mary K. Townsend; Stephanie Tissot; Sylvie Rusakiewicz; Humberto J. Ferreira; Anne I. Kraemer; Michal Bassani‐Sternberg; Elizabeth M. Swisher; Lana Elias Kandalaft; Spyridon Alexandros Mastroyannis

doi:10.1016/j.ccell.2025.07.005

ImmunologyCancer CellJul 31, 2025

Peer-reviewed journal article

Myeloid cell networks determine reinstatement of original immune environments in recurrent ovarian cancer

Eleonora Ghisoni iD, Fabrizio Benedetti iD, Aspram Minasyan iD, Mathieu Desbuisson iD, Paula Cunnea iD, Alizée J Grimm iD, Noémie Fahr iD, Charlotte Capt, Nicolas Rayroux iD, Flavia De Carlo, D. C. Gulhan iD, Julien Dagher iD, David Barras iD, Matteo Morotti iD, Juan A. Marín‐Jiménez iD, Bovannak Stewen Chap iD, Tania Santoro, Giulia Spagnol iD, Mapi Fleury iD, Katerina Fortis, Julien Dorier iD, Mary K. Townsend iD, Stephanie Tissot, Sylvie Rusakiewicz iD, Humberto J. Ferreira iD, , Denarda Dangaj Laniti iD

Abstract

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 Brca1mut tumours maintained activated TILs:dendritic cells (DCs) niches and immunostimulatory tumour-associated macrophages (TAMs). Conversely, recurrent Brca1wt tumours displayed loss of TILs:DCs niches and accumulated immunosuppressive myeloid networks featuring Trem2/ApoEhigh TAMs and Nduf4l2high/Galectin3high 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.

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