The programmed death-1 immune-suppressive pathway: barrier to antitumor immunity

J Immunol. 2014 Oct 15;193(8):3835-41. doi: 10.4049/jimmunol.1401572.

Abstract

Programmed death ligand 1 (PD-L1, also known as B7 homolog 1 or CD274) is a major obstacle to antitumor immunity because it tolerizes/anergizes tumor-reactive T cells by binding to its receptor programmed death-1 (CD279), renders tumor cells resistant to CD8(+) T cell- and FasL-mediated lysis, and tolerizes T cells by reverse signaling through T cell-expressed CD80. PD-L1 is abundant in the tumor microenvironment, where it is expressed by many malignant cells, as well as by immune cells and vascular endothelial cells. The critical role of PD-L1 in obstructing antitumor immunity has been demonstrated in multiple animal models and in recent clinical trials. This article reviews the mechanisms by which PD-L1 impairs antitumor immunity and discusses established and experimental strategies for maintaining T cell activation in the presence of PD-L1-expressing cells in the tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology
  • B7-1 Antigen / immunology*
  • B7-H1 Antigen / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Fas Ligand Protein / immunology
  • Humans
  • Immune Tolerance*
  • Lymphocyte Activation / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Neoplasms / immunology*
  • Programmed Cell Death 1 Receptor / immunology*
  • Signal Transduction / immunology
  • Tumor Microenvironment / immunology

Substances

  • B7-1 Antigen
  • B7-H1 Antigen
  • Fas Ligand Protein
  • Programmed Cell Death 1 Receptor