PD-1/PD-L1 axis: implications in immune regulation, cancer progression, and translational applications

J Mol Med (Berl). 2024 Aug;102(8):987-1000. doi: 10.1007/s00109-024-02463-3. Epub 2024 Jun 27.

Abstract

The PD-1/PD-L1 axis is a complex signaling pathway that has an important role in the immune system cells. Programmed cell death protein 1 (PD-1) acts as an immune checkpoint on the T lymphocytes, B lymphocytes, natural killer (NK), macrophages, dendritic cells (DCs), monocytes, and myeloid cells. Its ligand, the programmed cell death 1 ligand (PD-L1), is expressed in the surface of the antigen-presenting cells (APCs). The binding of both promotes the downregulation of the T cell response to ensure the activation to prevent the onset of chronic immune inflammation. This axis in the tumor microenvironment (TME) performs a crucial role in the tumor progression and the escape of the tumor by neutralizing the immune system, the engagement of PD-L1 with PD-1 in the T cell causes dysfunctions, neutralization, and exhaustion, providing the tumor mass production. This review will provide a comprehensive overview of the functions of the PD-1/PD-L1 system in immune function, cancer, and the potential therapeutic implications of the PD-1/PD-L1 pathway for cancer management.

Keywords: Cancer; Immune checkpoint inhibitors (ICIs); PI3K/AKT pathway; Predictive biomarkers; Programmed cell death 1 ligand (PD-L1); Programmed cell death protein 1 (PD-1).

Publication types

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

MeSH terms

  • Animals
  • B7-H1 Antigen* / immunology
  • B7-H1 Antigen* / metabolism
  • Disease Progression
  • Humans
  • Immunomodulation
  • Neoplasms* / immunology
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Programmed Cell Death 1 Receptor* / immunology
  • Programmed Cell Death 1 Receptor* / metabolism
  • Signal Transduction
  • Translational Research, Biomedical
  • Tumor Microenvironment* / immunology

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • CD274 protein, human
  • PDCD1 protein, human