Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality
Abstract Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I–III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (H...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00721-2 |
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| author | Noor A. M. Bakker Hannah Garner Ewald van Dyk Elisa Champanhet Chris Klaver Maxime Duijst Leonie Voorwerk Iris Nederlof Rosie Voorthuis Marte C. Liefaard Marja Nieuwland Iris de Rink Onno B. Bleijerveld Hendrika M. Oosterkamp Lodewyk F. A. Wessels Marleen Kok Karin E. de Visser |
| author_facet | Noor A. M. Bakker Hannah Garner Ewald van Dyk Elisa Champanhet Chris Klaver Maxime Duijst Leonie Voorwerk Iris Nederlof Rosie Voorthuis Marte C. Liefaard Marja Nieuwland Iris de Rink Onno B. Bleijerveld Hendrika M. Oosterkamp Lodewyk F. A. Wessels Marleen Kok Karin E. de Visser |
| author_sort | Noor A. M. Bakker |
| collection | DOAJ |
| description | Abstract Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I–III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy. Vδ1 γδ T cells from mTNBC patients produced more IL17 than those from HDs. Chemotherapy-naïve mTNBC patients showed increased classical monocytes and neutrophils. Transcriptional, proteomic, and functional analyses revealed that neutrophils in mTNBC exhibited enhanced migratory capacity, elevated granule proteins, and higher ROS production. Some immune changes, such as reduced non-switched B cells and heightened neutrophil migration, were evident in earlier TNBC stages. This study comprehensively maps systemic immunity in TNBC, guiding future research on patient stratification and immunomodulation strategies. |
| format | Article |
| id | doaj-art-f1ae44950a6d4dcaa6d95e3a93f88194 |
| institution | Kabale University |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-f1ae44950a6d4dcaa6d95e3a93f881942025-01-26T12:45:45ZengNature Portfolionpj Breast Cancer2374-46772025-01-0111111710.1038/s41523-025-00721-2Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionalityNoor A. M. Bakker0Hannah Garner1Ewald van Dyk2Elisa Champanhet3Chris Klaver4Maxime Duijst5Leonie Voorwerk6Iris Nederlof7Rosie Voorthuis8Marte C. Liefaard9Marja Nieuwland10Iris de Rink11Onno B. Bleijerveld12Hendrika M. Oosterkamp13Lodewyk F. A. Wessels14Marleen Kok15Karin E. de Visser16Division of Tumor Biology & Immunology, The Netherlands Cancer InstituteDivision of Tumor Biology & Immunology, The Netherlands Cancer InstituteDivision of Tumor Biology & Immunology, The Netherlands Cancer InstituteDivision of Tumor Biology & Immunology, The Netherlands Cancer InstituteDivision of Tumor Biology & Immunology, The Netherlands Cancer InstituteDivision of Tumor Biology & Immunology, The Netherlands Cancer InstituteDivision of Tumor Biology & Immunology, The Netherlands Cancer InstituteDivision of Tumor Biology & Immunology, The Netherlands Cancer InstituteDivision of Molecular Pathology, The Netherlands Cancer InstituteDivision of Molecular Pathology, The Netherlands Cancer InstituteGenomics Core Facility, The Netherlands Cancer InstituteGenomics Core Facility, The Netherlands Cancer InstituteProteomics Facility, The Netherlands Cancer InstituteDepartment of Medical Oncology, Haaglanden Medical CenterOncode InstituteDivision of Tumor Biology & Immunology, The Netherlands Cancer InstituteDivision of Tumor Biology & Immunology, The Netherlands Cancer InstituteAbstract Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I–III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy. Vδ1 γδ T cells from mTNBC patients produced more IL17 than those from HDs. Chemotherapy-naïve mTNBC patients showed increased classical monocytes and neutrophils. Transcriptional, proteomic, and functional analyses revealed that neutrophils in mTNBC exhibited enhanced migratory capacity, elevated granule proteins, and higher ROS production. Some immune changes, such as reduced non-switched B cells and heightened neutrophil migration, were evident in earlier TNBC stages. This study comprehensively maps systemic immunity in TNBC, guiding future research on patient stratification and immunomodulation strategies.https://doi.org/10.1038/s41523-025-00721-2 |
| spellingShingle | Noor A. M. Bakker Hannah Garner Ewald van Dyk Elisa Champanhet Chris Klaver Maxime Duijst Leonie Voorwerk Iris Nederlof Rosie Voorthuis Marte C. Liefaard Marja Nieuwland Iris de Rink Onno B. Bleijerveld Hendrika M. Oosterkamp Lodewyk F. A. Wessels Marleen Kok Karin E. de Visser Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality npj Breast Cancer |
| title | Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality |
| title_full | Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality |
| title_fullStr | Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality |
| title_full_unstemmed | Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality |
| title_short | Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality |
| title_sort | triple negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality |
| url | https://doi.org/10.1038/s41523-025-00721-2 |
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