UNDERSTANDING, PREDICTING, AND IMPROVING IMMUNE CHECKPOINT BLOCKADE IMMUNOTHERAPY RESPONSE IN BLADDER CANCER

Immune checkpoint blockade immunotherapy (ICB) has increased survival for patients with locally advanced and metastatic bladder cancer, but few patients have enduring responses. To improve patient outcomes with ICB, we need to better understand and predict ICB responses, and we need to improve upon ICB with new treatment combinations. To better understand and predict ICB response, we analyzed clinical correlative data from patients treated with ICB. Then, we assessed the impact of tumor architecture on chemo-ICB response in muscle-invasive bladder cancer, developing predictive response models from spatial proteomic markers. We also analyzed molecular and immune data from muscle-invasive bladder cancer patients treated with chemo-ICB and identified features associated with changes during treatment and with response. Finally, we took steps toward improving ICB response by testing neoantigen vaccination with entinostat in a murine bladder cancer model. Our work furthers the field of bladder cancer immunotherapy and highlights important future research directions to improve bladder cancer precision medicine.