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Immune checkpoint blockade: the role of PD-1-PD-L axis in lymphoid malignancies

Authors Ilcus C, Bagacean C, Tempescul A, Popescu C, Parvu A, Cenariu M, Bocsan C, Zdrenghea M

Received 27 January 2017

Accepted for publication 31 March 2017

Published 28 April 2017 Volume 2017:10 Pages 2349—2363


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 5

Editor who approved publication: Dr Carlos E Vigil

Cristina Ilcus,1 Cristina Bagacean,1,2 Adrian Tempescul,3 Cristian Popescu,1 Andrada Parvu,1,4 Mihai Cenariu,5 Corina Bocsan,6,* Mihnea Zdrenghea1,4,*

1Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Laboratory of Immunology and Immunotherapy, Brest University Medical School, CHRU Morvan, 3Department of Clinical Hematology, Institute of Cancerology and Hematology, Brest, France; 4Department of Hematology, Ion Chiricuta Oncology Institute, 5Biotechnology Research Center, University of Agricultural Sciences and Veterinary Medicine, 6Department of Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

*These authors contributed equally to this work

Abstract: The co-inhibitory receptor programmed cell death (PD)-1, expressed by immune effector cells, is credited with a protective role for normal tissue during immune responses, by limiting the extent of effector activation. Its presently known ligands, programmed death ligands (PD-Ls) 1 and 2, are expressed by a variety of cells including cancer cells, suggesting a role for these molecules as an immune evasion mechanism. Blocking of the PD-1-PD-L signaling axis has recently been shown to be effective and was clinically approved in relapsed/refractory tumors such as malignant melanoma and lung cancer, but also classical Hodgkin’s lymphoma. A plethora of trials exploring PD-1 blockade in cancer are ongoing. Here, we review the role of PD-1 signaling in lymphoid malignancies, and the latest results of trials investigating PD-1 or PD-L1 blocking agents in this group of diseases. Early phase studies proved very promising, leading to the clinical approval of a PD-1 blocking agent in Hodgkin’s lymphoma, and Phase III clinical studies are either planned or ongoing in most lymphoid malignancies.

Keywords: immune checkpoint blockade, programmed cell death 1, b7 antigens, hematological cancer, lymphoma, chronic lymphocytic leukemia

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