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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Veröffentlicht in:Neoplasia (New York, N.Y.) Jg. 60; S. 101130
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 01.02.2025
Elsevier
Schlagworte:
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
Online-Zugang:Volltext
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1476-5586
1476-5586
DOI:10.1016/j.neo.2025.101130