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Journal of molecular medicine (Berlin, Germany)
08, 2024;102 (8): 987-1000.

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

Miguel A Ortega, Diego Liviu Boaru, Diego De Leon-Oliva, Oscar Fraile-Martinez, Cielo García-Montero, Laura Rios, Maria J Garrido-Gil, Silvestra Barrena-Blázquez, Ana M Minaya-Bravo, Antonio Rios-Parra, Melchor Álvarez-Mon, Laura Jiménez-Álvarez, Laura López-González, Luis G Guijarro, Raul Diaz, Miguel A Saez
Author Information
  1. Miguel A Ortega: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain. miguelangel.ortega@uah.es. ORCID
  2. Diego Liviu Boaru: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  3. Diego De Leon-Oliva: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  4. Oscar Fraile-Martinez: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  5. Cielo García-Montero: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  6. Laura Rios: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  7. Maria J Garrido-Gil: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  8. Silvestra Barrena-Blázquez: Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain.
  9. Ana M Minaya-Bravo: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  10. Antonio Rios-Parra: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  11. Melchor Álvarez-Mon: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  12. Laura Jiménez-Álvarez: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  13. Laura López-González: Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain.
  14. Luis G Guijarro: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
  15. Raul Diaz: Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain. raul.diazp@uah.es.
  16. Miguel A Saez: Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, CIBEREHD, University of Alcalá, 28801, Alcala de Henares, Spain.
PMID: 38935130 DOI: 10.1007/s00109-024-02463-3

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)

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Grants

  1. MITIC-CM/Comunidad de Madrid

MeSH Term

Humans
Neoplasms
B7-H1 Antigen
Programmed Cell Death 1 Receptor
Animals
Tumor Microenvironment
Signal Transduction
Disease Progression
Immunomodulation
Translational Research, Biomedical

Chemicals

B7-H1 Antigen
Programmed Cell Death 1 Receptor
CD274 protein, human
PDCD1 protein, human
Journal Article Review Research Support, Non-U.S. Gov't
Article has an altmetric score of 6

Word Cloud

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