New Strategies in Bladder Cancer: A Second Coming for Immunotherapy

Abstract

Urothelial bladder cancer (UBC) remains one of the most common and deadly cancers worldwide, and platinum-based chemotherapy, which has been the standard-of-care in metastatic bladder cancer, has had limited success in improving outcomes for patients. The recent development and translation of therapeutic strategies aimed at harnessing the immune system have led to durable and prolonged survival for patients with several different cancers, including UBC. In this review, we discuss new findings in bladder cancer immunotherapy, including recent successes with immune checkpoint blockade. We also discuss therapeutic cancer vaccines and highlight several additional immunotherapy modalities in early stages of development.

Figure 1

Mechanism of action of selected immunotherapies in urothelial bladder cancer. A) Representation of cellular interactions within the lymph node. Adaptive immune responses initiate at the lymph node through the interaction of T cells and dendritic cells (DC). Vaccines initiate an immune response by providing target antigens to DCs and triggering their activation. Activated DCs in turn present antigen as well as co-stimulatory molecules and immune checkpoints to T cells. These molecules shape the quality and magnitude of the T cell response. B) In the tumor microenvironment, T cells encounter cognate antigen and can cause tumor lysis. However, tumors often express inhibitory immune checkpoint molecules such as PD-L1 to inhibit T cell responses. In addition to the tumor cells themselves, tumor-associated macrophages can also inhibit T cell responses through a variety of mechanisms including immune checkpoint expression and metabolic inhibition.