The dynamic immune behavior of primary and metastatic ovarian carcinoma

Abstract Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a co...

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Main Authors: Elaine Stur, Fuduan Peng, Pang-ning Teng, Emine Bayraktar, Min Hu, Sara Corvigno, David J. Brown, Sanghoon Lee, Kathleen N. Moore, Nicholas W. Bateman, Kathleen M. Darcy, George L. Maxwell, Thomas P. Conrads, Nidhi Sahni, Ignacio Vázquez-García, Sohrab P. Shah, Joseph Celestino, Nicole D. Fleming, Nicholas E. Navin, Linghua Wang, Anil K. Sood
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00818-8
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Summary:Abstract Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, we found that untreated primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation; this, in turn, was correlated with expression changes in the interferon α and γ pathways in epithelial cells, showing that cross-communication between the epithelial and immune compartments is important for immune suppression in HGSC. These findings could have implications for the design of clinical trials with immune-modulating drugs.
ISSN:2397-768X