The dynamic immune behavior of primary and metastatic ovarian carcinoma
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.
Authors
- Nicholas W. Bateman (ORCID: https://orcid.org/0000-0002-4425-9511)
- George L. Maxwell
- Emine Bayraktar (ORCID: https://orcid.org/0000-0002-5189-1507)
- Fuduan Peng (ORCID: https://orcid.org/0000-0003-4068-530X)
- Sohrab P. Shah (ORCID: https://orcid.org/0000-0001-6402-523X)
- Sara Corvigno (ORCID: https://orcid.org/0000-0001-5458-2243)
- Pang-ning Teng (ORCID: https://orcid.org/0000-0002-7919-3567)
- Elaine Stur (ORCID: https://orcid.org/0000-0001-5962-0050)
- Ignacio Vázquez-Garćıa (ORCID: https://orcid.org/0000-0003-0427-2639)
- Linghua Wang (ORCID: https://orcid.org/0000-0001-9380-0266)
- Nidhi Sahni (ORCID: https://orcid.org/0000-0002-9155-5882)
- Joseph Celestino (ORCID: https://orcid.org/0000-0002-7758-1558)
- Nicholas E. Navin (ORCID: https://orcid.org/0000-0002-2106-8624)
- Kathleen N. Moore (ORCID: https://orcid.org/0000-0002-5803-0718)
- Min Hu (ORCID: https://orcid.org/0009-0000-0058-5289)
- David J. Brown (ORCID: https://orcid.org/0000-0002-4015-7382)
- Thomas P. Conrads (ORCID: https://orcid.org/0000-0003-4742-3281)
- Kathleen M. Darcy (ORCID: https://orcid.org/0000-0003-2888-2968)
- Nicole D. Fleming (ORCID: https://orcid.org/0000-0003-1785-4072)
- Sanghoon Lee (ORCID: https://orcid.org/0000-0002-5546-0763)
- Anil K. Sood (ORCID: https://orcid.org/0000-0003-4242-1762)
Institutions
- Broad Institute (US)
- Inova Health System (US)
- Henry M. Jackson Foundation (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- Baylor College of Medicine (US)
- Walter Reed National Military Medical Center (US)
- Massachusetts General Hospital (US)
- Quantitative BioSciences (US)
- Center for Cancer Research (US)
- University of Oklahoma Health Sciences Center (US)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1038/s41698-025-00818-8
- Citations
- 4
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 3.19
Funders
- Cancer Prevention and Research Institute of Texas
- Frank McGraw Memorial Chair in Cancer Research
- Ovarian Cancer Research Alliance
- Uniformed Services University of the Health Sciences
- University of Texas MD Anderson Cancer Center