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Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Stockholm South General Hospital, Karolinska Institutet, Stockholm, Sweden.
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2017 (English)In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 176, 63-70 p.Article in journal (Refereed) Published
Abstract [en]

Cancer is currently treated by a combination of therapies, including chemotherapy which is believed to suppress the immune system. Combination of immunotherapy and chemotherapy correlates with improved survival but needs careful planning in order to achieve a synergistic effect. In this study, we have demonstrated that doxorubicin treatment of B cells resulted in increased expression of CD86 and concordantly increased CD4(+) T cell activation in the presence of superantigen, an effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore, doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-10 and TNF-α. Finally, B cells from urinary bladder cancer patients, treated with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-expression. We conclude that doxorubicin induces CD86 expression on B cells and hence enhances their antigen-presenting ability in vitro, a finding verified in patients. Development of tailored time and dose schedules may increase the effectiveness of combining chemotherapy and immunotherapy.

Place, publisher, year, edition, pages
2017. Vol. 176, 63-70 p.
Keyword [en]
Doxorubicin, Bcells, Immunology, Urinary bladder cancer, Neoadjuvant chemotherapy, CD86
National Category
Urology and Nephrology
Identifiers
URN: urn:nbn:se:umu:diva-131335DOI: 10.1016/j.clim.2016.12.003ISI: 000396965200008PubMedID: 28025135OAI: oai:DiVA.org:umu-131335DiVA: diva2:1073701
Funder
Swedish Research Council, VLL-582631
Available from: 2017-02-13 Created: 2017-02-13 Last updated: 2017-05-10Bibliographically approved

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