Programmed death-1 pathway in cancer and autoimmunity.
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.
Department of Medicine, New York University School of Medicine, NY, USA.
Ariel
A
Pedoeem
Department of Medicine, New York University School of Medicine, NY, USA.
Inbar
I
Azoulay-Alfaguter
Department of Medicine, New York University School of Medicine, NY, USA.
Marianne
M
Strazza
Department of Medicine, New York University School of Medicine, NY, USA; Department of Pathology, New York University School of Medicine, NY, USA.
Gregg J
GJ
Silverman
Department of Medicine, New York University School of Medicine, NY, USA; Department of Pathology, New York University School of Medicine, NY, USA. Electronic address: Adam.Mor@NYUMC.org.
Adam
A
Mor
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003141:Communicable Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D008024:Ligands; D061026:Programmed Cell Death 1 Receptor
Adhesion; Autoimmunity; Programmed death-1; T cells