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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/223347
Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer
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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.
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GHISONI, Eleonora, et al. Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer. Cancer Cell. 2025. Vol. 43, num. 8, pags. 1568-1586. ISSN 1878-3686. [consulted: 5 of October of 2026]. Available at: https://hdl.handle.net/2445/223347