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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Vydané v:	Neoplasia (New York, N.Y.) Ročník 60; s. 101130
Hlavní autori:	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:	English
Vydavateľské údaje:	United States Elsevier Inc 01.02.2025 Elsevier
Predmet:	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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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.
AbstractList	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.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. 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.
ArticleNumber	101130
Author	Pham, Thuý An Dreyer, Tobias F. Wohlleber, Dirk Steiger, Katja Stange, Christoph Weichert, Wilko Magdolen, Viktor Sauter-Peschke, Dominique Anton, Martina Multhoff, Gabriele Kiechle, Marion Seitz, Stefanie Reuning, Ute Bronger, Holger
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Snippet	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...
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SubjectTerms	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
Title	The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer
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