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CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer

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CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer. / Bronger, Holger; Singer, Judith; Windmüller, Claudia; Reuning, Ute; Zech, Daniela; Delbridge, Claire; Dorn, Julia; Kiechle, Marion; Schmalfeldt, Barbara; Schmitt, Manfred; Avril, Stefanie.

in: BRIT J CANCER, Jahrgang 115, Nr. 5, 23.08.2016, S. 553-63.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Bronger, H, Singer, J, Windmüller, C, Reuning, U, Zech, D, Delbridge, C, Dorn, J, Kiechle, M, Schmalfeldt, B, Schmitt, M & Avril, S 2016, 'CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer', BRIT J CANCER, Jg. 115, Nr. 5, S. 553-63. https://doi.org/10.1038/bjc.2016.172

APA

Bronger, H., Singer, J., Windmüller, C., Reuning, U., Zech, D., Delbridge, C., Dorn, J., Kiechle, M., Schmalfeldt, B., Schmitt, M., & Avril, S. (2016). CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer. BRIT J CANCER, 115(5), 553-63. https://doi.org/10.1038/bjc.2016.172

Vancouver

Bronger H, Singer J, Windmüller C, Reuning U, Zech D, Delbridge C et al. CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer. BRIT J CANCER. 2016 Aug 23;115(5):553-63. https://doi.org/10.1038/bjc.2016.172

Bibtex

@article{4e8e51540d0246b083fb593cd97a4053,
title = "CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer",
abstract = "BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic recruitment of TILs, and their intratumoral accumulation is a conceivable way to improve TIL-dependent immune intervention in cancer. However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian cancer (HGSC) is largely unknown.METHODS: One hundred and eighty four cases of HGSC were immunohistochemically analyzed for CXCL9, CXCL10. TILs were assessed using CD3, CD56 and FOXP3 staining. Chemokine regulation was investigated using the ovarian cancer cell lines OV-MZ-6 and SKOV-3.RESULTS: High expression of CXCL9 and CXCL10 was associated with an approximately doubled overall survival (n=70, CXCL9: HR 0.41; P=0.006; CXCL10: HR 0.46; P=0.010) which was confirmed in an independent validation set (n=114; CXCL9: HR 0.60; P=0.019; CXCL10: HR 0.52; P=0.005). Expression of CXCR3 ligands significantly correlated with TILs. In human ovarian cancer cell lines the cyclooxygenase (COX) metabolite Prostaglandin E2 was identified as negative regulator of chemokine secretion, whereas COX inhibition by indomethacin significantly upregulated CXCL9 and CXCL10. In contrast, celecoxib, the only COX inhibitor prospectively evaluated for therapy of ovarian cancer, suppressed NF-κB activation and inhibited chemokine release.CONCLUSION: Our results support the notion that CXCL9 and CXCL10 exert tumour-suppressive function by TIL recruitment in human ovarian cancer. COX inhibition by indomethacin, not by celecoxib, may be a promising approach to concomitantly improve immunotherapies.",
keywords = "Journal Article",
author = "Holger Bronger and Judith Singer and Claudia Windm{\"u}ller and Ute Reuning and Daniela Zech and Claire Delbridge and Julia Dorn and Marion Kiechle and Barbara Schmalfeldt and Manfred Schmitt and Stefanie Avril",
year = "2016",
month = aug,
day = "23",
doi = "10.1038/bjc.2016.172",
language = "English",
volume = "115",
pages = "553--63",
journal = "BRIT J CANCER",
issn = "0007-0920",
publisher = "NATURE PUBLISHING GROUP",
number = "5",

}

RIS

TY - JOUR

T1 - CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer

AU - Bronger, Holger

AU - Singer, Judith

AU - Windmüller, Claudia

AU - Reuning, Ute

AU - Zech, Daniela

AU - Delbridge, Claire

AU - Dorn, Julia

AU - Kiechle, Marion

AU - Schmalfeldt, Barbara

AU - Schmitt, Manfred

AU - Avril, Stefanie

PY - 2016/8/23

Y1 - 2016/8/23

N2 - BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic recruitment of TILs, and their intratumoral accumulation is a conceivable way to improve TIL-dependent immune intervention in cancer. However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian cancer (HGSC) is largely unknown.METHODS: One hundred and eighty four cases of HGSC were immunohistochemically analyzed for CXCL9, CXCL10. TILs were assessed using CD3, CD56 and FOXP3 staining. Chemokine regulation was investigated using the ovarian cancer cell lines OV-MZ-6 and SKOV-3.RESULTS: High expression of CXCL9 and CXCL10 was associated with an approximately doubled overall survival (n=70, CXCL9: HR 0.41; P=0.006; CXCL10: HR 0.46; P=0.010) which was confirmed in an independent validation set (n=114; CXCL9: HR 0.60; P=0.019; CXCL10: HR 0.52; P=0.005). Expression of CXCR3 ligands significantly correlated with TILs. In human ovarian cancer cell lines the cyclooxygenase (COX) metabolite Prostaglandin E2 was identified as negative regulator of chemokine secretion, whereas COX inhibition by indomethacin significantly upregulated CXCL9 and CXCL10. In contrast, celecoxib, the only COX inhibitor prospectively evaluated for therapy of ovarian cancer, suppressed NF-κB activation and inhibited chemokine release.CONCLUSION: Our results support the notion that CXCL9 and CXCL10 exert tumour-suppressive function by TIL recruitment in human ovarian cancer. COX inhibition by indomethacin, not by celecoxib, may be a promising approach to concomitantly improve immunotherapies.

AB - BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic recruitment of TILs, and their intratumoral accumulation is a conceivable way to improve TIL-dependent immune intervention in cancer. However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian cancer (HGSC) is largely unknown.METHODS: One hundred and eighty four cases of HGSC were immunohistochemically analyzed for CXCL9, CXCL10. TILs were assessed using CD3, CD56 and FOXP3 staining. Chemokine regulation was investigated using the ovarian cancer cell lines OV-MZ-6 and SKOV-3.RESULTS: High expression of CXCL9 and CXCL10 was associated with an approximately doubled overall survival (n=70, CXCL9: HR 0.41; P=0.006; CXCL10: HR 0.46; P=0.010) which was confirmed in an independent validation set (n=114; CXCL9: HR 0.60; P=0.019; CXCL10: HR 0.52; P=0.005). Expression of CXCR3 ligands significantly correlated with TILs. In human ovarian cancer cell lines the cyclooxygenase (COX) metabolite Prostaglandin E2 was identified as negative regulator of chemokine secretion, whereas COX inhibition by indomethacin significantly upregulated CXCL9 and CXCL10. In contrast, celecoxib, the only COX inhibitor prospectively evaluated for therapy of ovarian cancer, suppressed NF-κB activation and inhibited chemokine release.CONCLUSION: Our results support the notion that CXCL9 and CXCL10 exert tumour-suppressive function by TIL recruitment in human ovarian cancer. COX inhibition by indomethacin, not by celecoxib, may be a promising approach to concomitantly improve immunotherapies.

KW - Journal Article

U2 - 10.1038/bjc.2016.172

DO - 10.1038/bjc.2016.172

M3 - SCORING: Journal article

C2 - 27490802

VL - 115

SP - 553

EP - 563

JO - BRIT J CANCER

JF - BRIT J CANCER

SN - 0007-0920

IS - 5

ER -