PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations

Hum Vaccin Immunother. 2019;15(5):1111-1122. doi: 10.1080/21645515.2019.1571892. Epub 2019 Mar 19.

Abstract

Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell checkpoint and plays a central role in regulating T cell exhaustion. Binding of PD-1 to its ligand, programmed death-ligand 1 (PD-L1), activates downstream signaling pathways and inhibits T cell activation. Moreover abnormally high PD-L1 expression on tumor cells and antigen-presenting cells in the tumor microenvironment mediates tumor immune escape, and the development of anti-PD-1/PD-L1 antibodies has recently become a hot topic in cancer immunotherapy. Here, we review the structure of PD-1 and PD-L1, the function of the PD-1/PD-L1 signaling pathway, the application of PD-1 or PD-L1 monoclonal antibodies and future directions for anti-PD-1/PD-L1 antibodies with combination therapies. Cancer immunotherapy using PD-1/PD-L1 immune checkpoint blockade may require more studies, and this approach may be curative for patients with many types of cancer in the future.

Keywords: PD-1; PD-L1; checkpoint; immunotherapy; tumor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / chemistry
  • B7-H1 Antigen / immunology*
  • Clinical Trials as Topic
  • Combined Modality Therapy / trends
  • Humans
  • Immunotherapy / trends*
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / chemistry
  • Programmed Cell Death 1 Receptor / immunology*
  • Signal Transduction
  • T-Lymphocytes / immunology
  • Tumor Microenvironment

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor

Grants and funding

This project was supported by grants from National Natural Science Foundation of China (No. 81671590) and National Basic Research Program of China (973 Program, No. 2014CB541803).