The role of PD-1 signaling in health and immune-related diseases

Front Immunol. 2023 May 16:14:1163633. doi: 10.3389/fimmu.2023.1163633. eCollection 2023.

Abstract

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance and provide immune homeostasis. Significantly, the binding partners of PD-1 and its associated ligands are diverse, which facilitates immunosuppression in cooperation with other immune checkpoint proteins. Accumulating evidence has demonstrated the important immunosuppressive role of the PD-1 axis in the tumor microenvironment and in autoimmune diseases. In addition, PD-1 blockades have been approved to treat various cancers, including solid tumors and hematological malignancies. Here, we provide a comprehensive review of the PD-1 pathway, focusing on the structure and expression of PD-1, programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2); the diverse biological functions of PD-1 signaling in health and immune-related diseases (including tumor immunity, autoimmunity, infectious immunity, transplantation immunity, allergy and immune privilege); and immune-related adverse events related to PD-1 and PD-L1 inhibitors.

Keywords: autoimmune diseases; immune checkpoint proteins; immune tolerance; immunotherapy; programmed cell death 1 receptor; tumor microenvironment.

Publication types

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

MeSH terms

  • Autoimmune Diseases* / drug therapy
  • Humans
  • Immunosuppression Therapy
  • Ligands
  • Neoplasms*
  • Programmed Cell Death 1 Receptor / metabolism
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • Programmed Cell Death 1 Receptor
  • Ligands

Grants and funding

This work was supported by the Suzhou Key Discipline Project of Pediatric Immunology (grant number SZXK202106); the Suzhou Science and Technology Development Plan Project (grant number SS202067); and the Suzhou Science and Technology Development Program Medical Devices and New Medicine (grant number SLT201941).