Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer

Clin Immunol. 2017 Mar;176:63-70. doi: 10.1016/j.clim.2016.12.003. Epub 2016 Dec 24.

Abstract

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.

Keywords: B cells; CD86; Doxorubicin; Immunology; Neoadjuvant chemotherapy; Urinary bladder cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • Antineoplastic Combined Chemotherapy Protocols / immunology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • B7-2 Antigen / immunology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Immunotherapy / methods
  • Interleukin-10 / immunology
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha / immunology
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / therapy*

Substances

  • B7-2 Antigen
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Doxorubicin