Journal
CLINICAL IMMUNOLOGY
Volume 176, Issue -, Pages 63-70Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2016.12.003
Keywords
Doxorubicin; B cells; Immunology; Urinary bladder cancer; Neoadjuvant chemotherapy; CD86
Categories
Funding
- Swedish Cancer Foundation [4-837/2015]
- Wallenberg Foundation
- Swedish Medical Research Council
- Regionala forskningsradet i Uppsala-Orebroregionen (RFR in Uppsala-Orebro) [RFR-313841]
- Swedish Research Council [VLL-582631]
- Cancer Research Foundation in Norrland, Umed, Sweden [CFF LP 15-2073]
- Karolinska Research Network Program in Immune Modulatory Therapies for Autoimmunity and Cancer
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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. (C) 2016 Published by Elsevier Inc.
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