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Programmed death-1/programmed death-1 ligand axis as a therapeutic target in oncology: current insights

Authors Schalper K, Venur V, Velcheti V

Received 21 July 2014

Accepted for publication 9 September 2014

Published 23 December 2014 Volume 2015:8 Pages 1—7


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Trevor W. Stone

Kurt A Schalper,1 Vyshak Alva Venur,2 Vamsidhar Velcheti2

1Department of Pathology, Yale University, New Haven, CT, 2Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH, USA

Abstract: Over the past few years, the functional modulation of immune-checkpoint pathways using monoclonal antibodies has emerged as a promising anticancer therapeutic strategy. A key mechanism utilized by tumor cells to induce immune tolerance is upregulation of the programmed death-1 (PD-1) pathway. PD-1 is a negative coregulatory receptor on T-cells and antigen-presenting cells. The PD-1 ligand (PD-L1) is expressed by several tumor types, and appears to be dynamically regulated by the immune microenvironment. Several investigational agents targeting either PD-1 or PD-L1 are under clinical development and show durable antitumor activity across several tumor types. This review summarizes the conceptual basis, safety, and clinical activity of currently available PD-1 pathway therapeutic antibodies.

Keywords: immunotherapy, cancer, biomarkers, immune-checkpoint inhibitors, programmed death receptor

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