Immunotherapies work by activating a patient’s own immune system to fight their cancer. Although immunotherapies can treat bladder cancer, most patients are not cured by these treatments. One reason that immunotherapies are not more effective is because of a specific type of immune cell, called macrophages, found in tumors where they can weaken the immune response and help tumors grow. Prior efforts to remove these cells or convert them into helpful ones have failed because we do not fully understand the biology of macrophages in bladder cancer.

Our goal is to develop a better understanding of the different types of macrophages and what they do in the tumor. In the first part of this study, we will examine patient tumor samples to learn how different types of macrophages affect the immune system and patient outcomes. We will use state-of-the-art approaches to look at gene activity in individual cells and their locations in the tumor. In the second part of this proposal, we will use human cells in culture and animal tumor models to study a new drug, FX-909 from Flare Therapeutics, which has shown promise to treat patients with bladder cancer in ongoing clinical trials. FX-909 targets a protein that is important to both cancer cells and harmful TAMs. We will work to understand if FX-909 helps the immune system fight cancer and determine if this drug is more effective when combined with current immunotherapies.

Overall, this research will help us better understand how macrophages support bladder cancer growth and how to target them with new treatments. Our goal is to develop new macrophage-targeted immunotherapies so that more bladder cancer patients will benefit from immunotherapy.