Programmed death-1 pathway in cancer and autoimmunity

Clin Immunol. 2014 Jul;153(1):145-52. doi: 10.1016/j.clim.2014.04.010. Epub 2014 Apr 26.


Programmed death-1 (PD-1) is a co-receptor that is expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system. A major functional role of the PD-1 signaling pathway is the inhibition of self-reactive T cells, which serve to protect against autoimmune diseases. Elimination of the PD-1 pathway can therefore result in the breakdown of immune tolerance that can ultimately lead to the development of pathogenic autoimmunity. Conversely, tumor cells can at times co-opt the PD-1 pathway to escape from immunosurveillance mechanisms. Therefore, blockade of the PD-1 pathway has become an attractive target in cancer therapy. Recent clinical trials have shown that anti-PD-1 agents have profound effects on solid tumor regression. Current approaches include six agents that are either PD-1 and PD-L1 targeted neutralizing antibodies or fusion proteins. More than forty clinical trials are underway to better define the role of PD-1 blockade in variety of tumor types. In this review we will highlight the basic biology of the PD-1 system and discuss its potential roles in both autoimmunity and cancer. We propose that future research on PD-1 may lead to the translation of fundamental regulatory pathways into the development of practical new approaches for the treatment of autoimmune diseases and cancer.

Keywords: Adhesion; Autoimmunity; Programmed death-1; T cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmunity*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Communicable Diseases / drug therapy
  • Communicable Diseases / genetics
  • Communicable Diseases / immunology
  • Communicable Diseases / metabolism
  • Humans
  • Ligands
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism*
  • Signal Transduction*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism


  • Ligands
  • Programmed Cell Death 1 Receptor