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Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer
Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
Umeå Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden; Karolinska Inst, Stockholm South Gen Hosp, Dept Urol, Stockholm, Sweden.
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2017 (English)In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 176, p. 63-70Article 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-alpha. 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, p. 63-70
Keywords [en]
Doxorubicin, B cells, Immunology, Urinary bladder cancer, Neoadjuvant chemotherapy, CD86
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
URN: urn:nbn:se:uu:diva-320835DOI: 10.1016/j.clim.2016.12.003ISI: 000396965200008PubMedID: 28025135OAI: oai:DiVA.org:uu-320835DiVA, id: diva2:1091453
Funder
Swedish Cancer Society, 4-837/2015Swedish Research Council, VLL-582631The Karolinska Institutet's Research FoundationAvailable from: 2017-04-26 Created: 2017-04-26 Last updated: 2018-07-13Bibliographically approved

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Holmström, BennyHansson, Johan

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