The Role of Interleukin?10 in Suppression of Bacillus Calmette?Guérin Induced T Helper Type 1Immune Response and Anti-Bladder Cancer Immunity

Bladder cancer is a common urologic cancer and intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the mainstay in the treatment of superficial bladder cancer. However, the current BCG therapy is not optimal with respect to its efficacy and side effects. Accumulating evidence suggests that proper induction of T helper type (Th) 1 immunity is required for effective immunotherapy of bladder cancer with BCG. Interleukin (IL)?10, a Th2 cytokine, down?regulates the Th1 immune response and is associated with BCG therapy failure. Therefore, blocking IL?10 activity could be beneficial for bladder cancer patients undergoing BCG therapy. We evaluated BCG in combination with IL? 10 neutralizing or receptor 1 (IL?10R1) blocking monoclonal antibodies (mAb) and found that the combination therapies induced enhanced Th1 immune responses and anti?bladder cancer immunity in preclinical animal models. The mechanistic studies revealed that BCG in combination with anti?IL?10R1 mAb induced specific antitumor immune responses. Our observations suggest that BCG immunotherapy for bladder cancer can be enhanced by addition of IL? 10 blocking agents. This paper reviews our recent progress in animal studies on bladder cancer treatment by BCG and IL?10 blocking agent combination therapies.