Abstract B087: MHC class II on cancer cells—Role in response to BCG therapy of bladder cancer

BCG, a live mycobacterium also used worldwide as a vaccine against tuberculosis, is one of the first successful immunotherapies of cancer. Despite being in clinical use for the treatment of non-muscle-invasive bladder cancer (NMIBC) for 4 decades, the mechanism by which BCG activates the immune system to destroy cancer cells is poorly understood and there are no reliable methods to predict a patient’s response to BCG treatment. Current data suggest that the efficacy of BCG depends on initial attachment of BCG to bladder cancer cells leading to activation of an immune response that is T-cell dependent. It is not known whether bladder cancer cells have a direct role in activating T-cells. Using an orthotopic mouse model of BCG treatment of bladder cancer we show that: 1) BCG induces tumor-specific immunity; 2) CD4+ T-cells are the main requirement for BCG efficacy and for the tumor-specific immunity engendered by BCG therapy;3) bladder cancer cells can directly activate CD4+ T-cells; 4) the efficacy of BCG depends on MHC class II expression on the surface of bladder cancer cells. These data suggest that bladder cancer cells directly activate and drive a CD4+ T-cell dependent immune response that is required for the efficacy of BCG. Current work in the lab is focused on characterizing MHC class II expression on human NMIBC specimens and determining whether expression of MHC class II on bladder cancer cells predicts clinical outcomes after BCG therapy. Citation Format: Gil Redelman-Sidi, Michael Glickman, Anna Binyamin, Anthony Antonelli. MHC class II on cancer cells—Role in response to BCG therapy of bladder cancer [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B087.