1. The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer
- Author
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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, and Holger Bronger
- Subjects
Chemokines ,CX3CL1 ,Tumour-infiltrating lymphocytes ,PARP inhibition ,Mouse model ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
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.
- Published
- 2025
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