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

Programmed death-1 pathway in cancer and autoimmunity.

Author information

1
Department of Medicine, New York University School of Medicine, NY, USA.
2
Department of Medicine, New York University School of Medicine, NY, USA; Department of Pathology, New York University School of Medicine, NY, USA.
3
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.

Abstract

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

PMID:
24780173
DOI:
10.1016/j.clim.2014.04.010
[Indexed for MEDLINE]

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