Emerging immunotherapies for bladder cancer

Abstract

Purpose of review: Inhibition of immune escape mechanisms, such as the programed death-ligand 1 pathway, has demonstrated rapid, durable responses in multiple tumor types, including advanced urothelial carcinoma. This review discusses emerging immunotherapies for urothelial carcinoma in various stages of clinical development.

Recent findings: Urothelial carcinoma has a high mutational burden, which may increase the number of tumor antigens and potentially enhance the ability of the immune system to recognize tumor cells as foreign. However, urothelial carcinoma can evade the immune system by downregulating tumor-antigen presentation, upregulating various immune checkpoints, and inactivating cytotoxic T cells. Immunotherapies for urothelial carcinoma target each of these steps to restore immune-mediated cytotoxicity. Many of these agents are in clinical trials for urothelial carcinoma.

Summary: Immunotherapies are active in urothelial carcinoma, but only in a fraction of patients, implying the presence of persistent immune escape. Identifying the mechanisms of immune escape and developing rational combinatorial regimens may make the benefit of immunotherapy accessible to a broader population.

Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures

FIGURE 1.

Urothelial carcinoma-specific antitumor T-cell immunity (modified from Chen and Mellman [22■]). 1. Released bladder tumor antigens. 2. Antigen processing and presentation. 3. Tumor antigen-specific T-cell priming, activation, and expansion. 4. Cytotoxic T-cell trafficking and infiltration to the tumor microenvironment. 5. T-cell recognition and immune-mediated tumor-cell killing.