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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Vydáno v:	Neoplasia (New York, N.Y.) Ročník 60; s. 101130
Hlavní autoři:	Seitz, Stefanie, Dreyer, Tobias F., Stange, Christoph, Steiger, Katja, Wohlleber, Dirk, Anton, Martina, Pham, Thuý An, Sauter-Peschke, Dominique, Reuning, Ute, Multhoff, Gabriele, Weichert, Wilko, Kiechle, Marion, Magdolen, Viktor, Bronger, Holger
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 01.02.2025 Elsevier
Témata:	Animals Cell Line, Tumor Cell Proliferation Chemokine CX3CL1 - genetics Chemokine CX3CL1 - metabolism Chemokines CX3CL1 Disease Models, Animal Female Humans Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism Mice Mouse model Ovarian Neoplasms - genetics Ovarian Neoplasms - immunology Ovarian Neoplasms - metabolism Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology PARP inhibition T-Lymphocytes - immunology T-Lymphocytes - metabolism Tumour-infiltrating lymphocytes Xenograft Model Antitumor Assays Mouse model Chemokines CX3CL1 Tumour-infiltrating lymphocytes PARP inhibition
ISSN:	1476-5586, 1476-5586
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1476-5586 1476-5586
DOI:	10.1016/j.neo.2025.101130