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

作者：Zirakzadeh A Ali; Kinn Johan; Krantz David; Rosenblatt Robert; Winerdal Malin E; Hu Jin; Hartana Ciputra Adijaya; Lundgren Christian; Bergman Emma Ahlen; Johansson Markus; Holmstrom Benny; Hansson Johan; Sidikii Alexander; Vasko Janos; Marits Per; Sherif Amir; Winqvist Ola^*

来源：Clinical Immunology, 2017, 176: 63-70.

DOI：10.1016/j.clim.2016.12.003

• Doxorubicin
• B cells
• Immunology
• Urinary bladder cancer
• Neoadjuvant chemotherapy
• CD86

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.

• 出版日期2017-3