A Review of the PD-1/PD-L1 Checkpoint in Bladder Cancer: From Mediator of Immune Escape to Target for Treatment

Urol Oncol. 2017 Jan;35(1):14-20. doi: 10.1016/j.urolonc.2016.10.004. Epub 2016 Nov 3.

Abstract

Purpose: Recent observations have focused attention on the means that human tumors employ to evade host defense systems critical to immune surveillance. The concepts of immunotherapy are familiar to urologists because of the use of bacillus Calmette-Guérin in bladder cancer. Research demonstrating the importance of checkpoint inhibitors in suppressing immune responses against tumors has heightened interest in immunotherapy at a time when there is a need for alternatives to bacillus Calmette-Guérin. We review the literature on the application of immunotherapeutic agents targeting a key checkpoint pathway, programmed death 1 (PD-1) and its ligand (PD-L1), in the field of bladder cancer.

Materials and methods: A comprehensive literature review was performed using Medline/Pubmed and Embase.

Results: The PD-1/PD-L1 pathway may be manipulated by cancer cells to subvert the immune system. PD-1/PD-L1 blockade has been tested in clinical trials for various malignancies including metastatic urothelial carcinoma, with significant response rates and limited side effects. PD-L1 expression has also been proposed as a prognostic marker for bladder cancer with mixed results.

Conclusions: PD-1 is one of several key receptors mediating immune escape, and agents targeting its ligand PD-L1 have already been successfully applied to patients with metastatic urothelial cancer. More research is needed to standardize criteria for PD-L1 positivity, explore its use as a biomarker, and optimize its use in the treatment for bladder cancer.

Keywords: BCG failure; Biomarker; Bladder cancer; Immunotherapy; PD-1; PD-L1.

Publication types

  • Review

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / metabolism
  • BCG Vaccine / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / immunology
  • Humans
  • Immunotherapy / methods*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Tumor Escape
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • BCG Vaccine
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • atezolizumab
  • pembrolizumab