Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives

Abstract

Bladder cancer is one of the most significant genitourinary cancer, causing high morbidity and mortality in a great number of patients. Over the years, various treatment methods for this type of cancer have been developed. The most common is the highly efficient method using Bacillus Calmette-Guerin, giving a successful effect in a high percentage of patients. However, due to the genetic instability of bladder cancer, together with individual needs of patients, the search for different therapy methods is ongoing. Immune checkpoints are cell surface molecules influencing the immune response and decreasing the strength of the immune response. Among those checkpoints, the PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death protein ligand 1) inhibitors aim at blocking those molecules, which results in T cell activation, and in bladder cancer the use of Atezolizumab, Avelumab, Durvalumab, Nivolumab, and Pembrolizumab has been described. The inhibition of another pivotal immune checkpoint, CTLA-4 (cytotoxic T cell antigen), may result in the mobilization of the immune system against bladder cancer and, among anti-CTLA-4 antibodies, the use of Ipilimumab and Tremelimumab has been discussed. Moreover, several different approaches to successful bladder cancer treatment exists, such as the use of ganciclovir and mTOR (mammalian target of rapamycin) kinase inhibitors, IL-12 (interleukin-12) and COX-2 (cyclooxygenase-2). The use of gene therapies and the disruption of different signaling pathways are currently being investigated. Research suggests that the combination of several methods increases treatment efficiency and the positive outcome in individual.

Keywords: bladder cancer; checkpoint inhibitor; immunotherapy.

Figure 1

Effect of checkpoint inhibitors in bladder cancer treatment. PD-1/PD-L1 and CTLA-4 blockers interfere with the immune system’s inhibitory checkpoint molecules, leading to T cell activation and tumor cell death. APC: antigen-presenting cells.