Tian C Zhou1, Alexander I Sankin2, Steven A Porcelli3, David S Perlin4, Mark P Schoenberg2, Xingxing Zang3. 1. Department of Urology, Montefiore Medical Center, Bronx, NY. Electronic address: tianc.zhou@gmail.com. 2. Department of Urology, Montefiore Medical Center, Bronx, NY. 3. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY. 4. Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ.
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.
PURPOSE: Recent observations have focused attention on the means that humantumors 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.
Authors: Eduardo Moreo; Santiago Uranga; Ana Picó; Ana Belén Gómez; Denise Nardelli-Haefliger; Carlos Del Fresno; Ingrid Murillo; Eugenia Puentes; Esteban Rodríguez; Mar Vales-Gómez; Julian Pardo; David Sancho; Carlos Martín; Nacho Aguilo Journal: J Immunother Cancer Date: 2022-07 Impact factor: 12.469
Authors: Italia Grenga; Renee N Donahue; Morgan L Gargulak; Lauren M Lepone; Mario Roselli; Marijo Bilusic; Jeffrey Schlom Journal: Urol Oncol Date: 2017-11-02 Impact factor: 3.498