The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer
T-cell recruiting chemokines are required for a successful immune intervention in ovarian cancer, and also for the efficacy of modern anticancer agents such as PARP inhibitors. The chemokine CX3CL1 recruits tumour-suppressive T-cells into solid tumours, but also mediates cell–cell adhesions, e.g. of...
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Elsevier
2025-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000090 |
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| author | Stefanie Seitz Tobias F. Dreyer Christoph Stange Katja Steiger Dirk Wohlleber Martina Anton Thuý An Pham Dominique Sauter-Peschke Ute Reuning Gabriele Multhoff Wilko Weichert Marion Kiechle Viktor Magdolen Holger Bronger |
| author_facet | Stefanie Seitz Tobias F. Dreyer Christoph Stange Katja Steiger Dirk Wohlleber Martina Anton Thuý An Pham Dominique Sauter-Peschke Ute Reuning Gabriele Multhoff Wilko Weichert Marion Kiechle Viktor Magdolen Holger Bronger |
| author_sort | Stefanie Seitz |
| collection | DOAJ |
| description | T-cell recruiting chemokines are required for a successful immune intervention in ovarian cancer, and also for the efficacy of modern anticancer agents such as PARP inhibitors. The chemokine CX3CL1 recruits tumour-suppressive T-cells into solid tumours, but also mediates cell–cell adhesions, e.g. of tumour cells, through its membrane-bound form. So far, its role in ovarian cancer has only been rudimentarily addressed. We show that high CX3CL1 expression significantly correlates with worsened survival in human high-grade serous ovarian cancer (n=219). In preclinical ovarian cancer, CX3CL1 plays a dual role, as it enhances the adaptive anti-tumour response, but overall still promotes tumour growth, the latter as a feature of the intraperitoneal environment. Moreover, PARP inhibitors are able to increase CX3CL1 release from human ovarian cancer cells. Collectively, our study shows that CX3CL1 is a driver of intraperitoneal tumour growth in ovarian cancer, a feature that may compromise the anticancer effect of CX3CL1-inducing PARP inhibitors. |
| format | Article |
| id | doaj-art-39f4087d4caa4b088d4e9c5baea8653b |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-39f4087d4caa4b088d4e9c5baea8653b2025-02-03T04:16:37ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-02-0160101130The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancerStefanie Seitz0Tobias F. Dreyer1Christoph Stange2Katja Steiger3Dirk Wohlleber4Martina Anton5Thuý An Pham6Dominique Sauter-Peschke7Ute Reuning8Gabriele Multhoff9Wilko Weichert10Marion Kiechle11Viktor Magdolen12Holger Bronger13Department of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, GermanyDepartment of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, GermanyDepartment of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, GermanyComparative Experimental Pathology, Institute of Pathology, Technical University of Munich, 81675 Munich, Germany; Institute of Pathology, Technical University of Munich, 81675 Munich, Germany; German Cancer Consortium (DKTK), partner site Munich, and German Cancer Research Center (DKFZ), Heidelberg, GermanyInstitute of Molecular Immunology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyInstitute of Molecular Immunology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, GermanyDepartment of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, GermanyDepartment of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, GermanyDepartment of Radiation Oncology, Technical University of Munich, TranslaTUM, 81675 Munich, GermanyInstitute of Pathology, Technical University of Munich, 81675 Munich, Germany; German Cancer Consortium (DKTK), partner site Munich, and German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, GermanyDepartment of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, GermanyDepartment of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, Germany; German Cancer Consortium (DKTK), partner site Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany; Corresponding author at: Department of Gynecology and Obstetrics, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany.T-cell recruiting chemokines are required for a successful immune intervention in ovarian cancer, and also for the efficacy of modern anticancer agents such as PARP inhibitors. The chemokine CX3CL1 recruits tumour-suppressive T-cells into solid tumours, but also mediates cell–cell adhesions, e.g. of tumour cells, through its membrane-bound form. So far, its role in ovarian cancer has only been rudimentarily addressed. We show that high CX3CL1 expression significantly correlates with worsened survival in human high-grade serous ovarian cancer (n=219). In preclinical ovarian cancer, CX3CL1 plays a dual role, as it enhances the adaptive anti-tumour response, but overall still promotes tumour growth, the latter as a feature of the intraperitoneal environment. Moreover, PARP inhibitors are able to increase CX3CL1 release from human ovarian cancer cells. Collectively, our study shows that CX3CL1 is a driver of intraperitoneal tumour growth in ovarian cancer, a feature that may compromise the anticancer effect of CX3CL1-inducing PARP inhibitors.http://www.sciencedirect.com/science/article/pii/S1476558625000090ChemokinesCX3CL1Tumour-infiltrating lymphocytesPARP inhibitionMouse model |
| spellingShingle | Stefanie Seitz Tobias F. Dreyer Christoph Stange Katja Steiger Dirk Wohlleber Martina Anton Thuý An Pham Dominique Sauter-Peschke Ute Reuning Gabriele Multhoff Wilko Weichert Marion Kiechle Viktor Magdolen Holger Bronger The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer Neoplasia: An International Journal for Oncology Research Chemokines CX3CL1 Tumour-infiltrating lymphocytes PARP inhibition Mouse model |
| title | The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer |
| title_full | The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer |
| title_fullStr | The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer |
| title_full_unstemmed | The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer |
| title_short | The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer |
| title_sort | chemokine cx3cl1 promotes intraperitoneal tumour growth despite enhanced t cell recruitment in ovarian cancer |
| topic | Chemokines CX3CL1 Tumour-infiltrating lymphocytes PARP inhibition Mouse model |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000090 |
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