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BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine

1
Division of Bacteriology, Medicines and Healthcare products Regulatory Agency-National Institute for Biological Standards and Control (MHRA-NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK
2
Department of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, 28049 Madrid, Spain
3
Hospital La Paz Institute for Health Research (IdiPAZ), Autonomous University of Madrid, 28046 Madrid, Spain
4
Urology Unit, Infanta Sofía Hospital, 28703 Madrid, Spain
5
Servicio de Urología, Hospital La Paz Institute for Health Research (IdiPAZ), 28046 Madrid, Spain
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(7), 940; https://doi.org/10.3390/cancers11070940
Received: 7 June 2019 / Revised: 26 June 2019 / Accepted: 28 June 2019 / Published: 4 July 2019
(This article belongs to the Special Issue Targeting Innate Immunity Cells in Cancer)
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Abstract

Background: Intra-vesical instillation of Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is an effective therapy for high-grade non-muscle invasive bladder cancer (NMIBC), which provokes a local immune response resulting in 70% of patients free of relapse after three years. Because non-responder patients usually have a bad prognosis, the early identification of treatment failure is crucial. We hypothesized that, if an effective immune response was taking place in the bladder, soluble factors would be released to the urine many days after BCG instillations. Methods: An extensive panel of cytokines and chemokines released into the urine seven days after every BCG instillation was screened in a cohort of NMIBC patients over three years. Results: The determinations of the urinary concentrations of cytokines, chemokines, and creatinine showed that increasing concentrations of C-X-C motif chemokine 10 (CXCL10) also known as interferon-inducible protein 10 (IP10) could be detected during the six-week induction cycle of BCG-treated patients released into the urine by CD14+ cells. In vitro, CXCL10 facilitated the recruitment of effector immune cells after the BCG-mediated upregulation of CXCR3 in both T- and natural killer (NK)-cells. Conclusions: The high concentrations of chemokine detected one week after the encounter with mycobacteria suggest that the CXCL10 axis might be related to the intensity of the immune anti-tumor response. View Full-Text
Keywords: cytokines; chemokines; NMIBC; BCG; biomarker cytokines; chemokines; NMIBC; BCG; biomarker
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Ashiru, O.; Esteso, G.; García‐Cuesta, E.M.; Castellano, E.; Samba, C.; Escudero-López, E.; López‐Cobo, S.; Álvarez-Maestro, M.; Linares, A.; Ho, M.M.; Leibar, A.; Martínez‐Piñeiro, L.; Valés‐Gómez, M. BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine. Cancers 2019, 11, 940.

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