A review of the PD-1/PD-l1 checkpoint in bladder cancer: from mediator of immune escape to target for treatment

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Abstract

Treatment of bladder cancer has evolved over time to include the traditional modalities of chemotherapy and surgery, and it has been greatly impacted by the use of immunotherapy. Modern immunotherapy focuses on checkpoint protein inhibitors, which are molecules impeding immune function, thereby allowing unregulated tumor cell growth and proliferation. Several immune checkpoint targets (programmed death ligand-1 [PD-L1], programmed cell death protein-1 [PD-1], and cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]) have received the most attention in the treatment of bladder cancer, whereas inhibitor agents have either been approved or are in late-stage development. This review describes the most recent data on PD-L1-inhibiting agents, found on the surface of tumor cells, and PD-1, found on activated T and B cells and macrophages. Aim. A review of modern PD-1 and PD-L1 inhibitors as target immunotherapeutic agents for the treatment of bladder cancer.

Materials and methods. We performed a comprehensive literature review using MEDLINE/PubMed and EMBASE.

Results. The PD-1/PD-L1 pathway is possibly manipulated by cancer cells to suppress 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 adverse effects. PD-L1 expression has mixed results as a prognostic marker for bladder cancer.

Conclusions. PD-1 is a key receptor mediating immune escape, and agents targeting its ligand, PD-L1, have already been successful in patients with metastatic urothelial cancer. Further research is warranted to standardize the criteria for PD-L1 positivity and to optimize its use in the treatment of bladder cancer.

About the authors

Andrey I. Gorelov

St. Petersburg State University

Author for correspondence.
Email: gorelov_a_i@mail.ru

Doctor of Medical Science, Professor, Department of Hospital Surgery

Russian Federation, Saint Petersburg

Andrei S. Simbirtsev

Institute of Highly Pure Biopreparations, FMBA of Russia

Email: gorelov_a_i@mail.ru

Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences, Scientific Supervisor

Russian Federation, Saint Petersburg

Dmitrii A. Zhuravskii

St. Petersburg State University

Email: zhuravskiy.spbu@gmail.com

Urologist

Russian Federation, Saint Petersburg

Anna A. Gorelova

Saint Petersburg State Research Institute of Phthisiopulmonology

Email: gorelov_a_i@mail.ru

Postgraduate

Russian Federation, Saint Petersburg

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Copyright (c) 2018 Gorelov A.I., Simbirtsev A.S., Zhuravskii D.A., Gorelova A.A.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
 


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