Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2025-08-11
Date Acceptance
2025-07-03
Citation
Cancer Cell, 2025, 43 (8), pp.1568-1586.e10
ISSN
1535-6108
Publisher
Elsevier BV
Start Page
1568
End Page
1586.e10
Journal / Book Title
Cancer Cell
Volume
43
Issue
8
Copyright Statement
© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Publication Status
Published
Date Publish Online
2025-07-31