Doxorubicin enhances the capacity of B cells to activate T cells in Urothelial Urinary Bladder Cancer

Publication date: Available online 24 December 2016
Source:Clinical Immunology
Author(s): A. Ali Zirakzadeh, Johan Kinn, David Krantz, Robert Rosenblatt, Malin E Winerdal, Jin Hu, Ciputra Adijaya Hartana, Christian Lundgren, Emma Ahlén Bergman, Markus Johansson, Benny Holmström, Johan Hansson, Alexander Sidikii, Janos Vasko, Per Marits, Amir Sherif, Ola Winqvist
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 presence of superantigen, an effect that was inhibited by 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 induce CD86 expression on B cells and hence enhance 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.



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