A review of the PD-1/PD-L1 checkpoint in bladder cancer: From mediator of immune escape to target for treatment

Tian C. Zhou, Alexander I. Sankin, Steven A. Porcelli, David S. Perlin, Mark P. Schoenberg, Xingxing Zang

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.

Original languageEnglish (US)
Pages (from-to)14-20
Number of pages7
JournalUrologic Oncology: Seminars and Original Investigations
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2017

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Urinary Bladder Neoplasms
Neoplasms
Mycobacterium bovis
Immunotherapy
Ligands
Immune System
Biological Markers
Clinical Trials
Carcinoma

Keywords

  • BCG failure
  • Biomarker
  • Bladder cancer
  • Immunotherapy
  • PD-1
  • PD-L1

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

A review of the PD-1/PD-L1 checkpoint in bladder cancer : From mediator of immune escape to target for treatment. / Zhou, Tian C.; Sankin, Alexander I.; Porcelli, Steven A.; Perlin, David S.; Schoenberg, Mark P.; Zang, Xingxing.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 35, No. 1, 01.01.2017, p. 14-20.

Research output: Contribution to journalReview article

Zhou, Tian C.; Sankin, Alexander I.; Porcelli, Steven A.; Perlin, David S.; Schoenberg, Mark P.; Zang, Xingxing / A review of the PD-1/PD-L1 checkpoint in bladder cancer : From mediator of immune escape to target for treatment.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 35, No. 1, 01.01.2017, p. 14-20.

Research output: Contribution to journalReview article

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AU - Perlin,David S.

AU - Schoenberg,Mark P.

AU - Zang,Xingxing

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N2 - 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.

AB - 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.

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