Immune checkpoint blockade therapy for bladder cancer treatment

Abstract

Bladder cancer remains the most immunogenic and expensive malignant tumor in the United States today. As the 4th leading cause of death from cancer in United States, Immunotherapy blocking immune checkpoints have been recently been applied to many aggressive cancers and changed interventions of urological cancers including advanced bladder cancer. The applied inhibition of PD-1-PD-L1 interactions can restore antitumor T-cell activity and enhance the cellular immune attack on antigens. The overall goals of this short review article are to introduce current cancer immunotherapy and immune checkpoint inhibitors, and to provide new insight into the underlying mechanisms that block immune checkpoints in tumor microenvironment. Furthermore, this review will address the preclinical and clinical trials to determine whether bladder cancer patients could benefit from this new cancer therapy in near future.

Keywords: Bladder cancer; Immune checkpoint; Immune therapy; PD-1; PD-L1.

Fig. 1. Tumor cells or tumor-infiltrating immune cells overexpress PD-L1 on their plasma membrane surface. PD-L1 binds to T-cell receptors (B7.1 or PD-1) in active T cells, deactivates cytotoxic T cells. Preventing PD-L1 from binding to its receptors on T cells makes T cells to remain active in tumor microenvironment.

Fig. 2. Examples of immune checkpoint blockade drugs for cancer treatment in development.