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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Nature Portfolio
2025-04-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00818-8 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Elaine Stur |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-24d29478f2ec4b759f3097901d128f5b |
| institution | DOAJ |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-24d29478f2ec4b759f3097901d128f5b2025-08-20T03:14:02ZengNature Portfolionpj Precision Oncology2397-768X2025-04-019111210.1038/s41698-025-00818-8The dynamic immune behavior of primary and metastatic ovarian carcinomaElaine Stur0Fuduan Peng1Pang-ning Teng2Emine Bayraktar3Min Hu4Sara Corvigno5David J. Brown6Sanghoon Lee7Kathleen N. Moore8Nicholas W. Bateman9Kathleen M. Darcy10George L. Maxwell11Thomas P. Conrads12Nidhi Sahni13Ignacio Vázquez-García14Sohrab P. Shah15Joseph Celestino16Nicole D. Fleming17Nicholas E. Navin18Linghua Wang19Anil K. Sood20Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterGynecologic Cancer Center of Excellence, The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Walter Reed National Military Medical CenterDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Genetics, The University of Texas MD Anderson Cancer CenterDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer CenterObstetrics and Gynecology, Stephenson Cancer Center, Stephenson Cancer Center at the University of Oklahoma Health Sciences Center/Sarah Cannon Research InstituteDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer CenterObstetrics and Gynecology, Stephenson Cancer Center, Stephenson Cancer Center at the University of Oklahoma Health Sciences Center/Sarah Cannon Research InstituteGynecologic Cancer Center of Excellence, The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Walter Reed National Military Medical CenterGynecologic Cancer Center of Excellence, The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Walter Reed National Military Medical CenterDepartment of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical CenterDepartment of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical CenterDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Baylor College of MedicineComputational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterComputational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center Department of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer CenterAbstract 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.https://doi.org/10.1038/s41698-025-00818-8 |
| spellingShingle | 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 The dynamic immune behavior of primary and metastatic ovarian carcinoma npj Precision Oncology |
| title | The dynamic immune behavior of primary and metastatic ovarian carcinoma |
| title_full | The dynamic immune behavior of primary and metastatic ovarian carcinoma |
| title_fullStr | The dynamic immune behavior of primary and metastatic ovarian carcinoma |
| title_full_unstemmed | The dynamic immune behavior of primary and metastatic ovarian carcinoma |
| title_short | The dynamic immune behavior of primary and metastatic ovarian carcinoma |
| title_sort | dynamic immune behavior of primary and metastatic ovarian carcinoma |
| url | https://doi.org/10.1038/s41698-025-00818-8 |
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