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

• Main Authors: Ilcus C, Bagacean C, Tempescul A, Popescu C, Parvu A, Cenariu M, Bocsan C, Zdrenghea M
• Format: Article
• Language: English
• Published: Dove Medical Press 2017-04-01
• Series: OncoTargets and Therapy
• Subjects: immune checkpoint blockade; programmed cell death 1; B7 antigens; hematological cancer; lymphoma; chronic lymphocytic leukemia
• Online Access: https://www.dovepress.com/immune-checkpoint-blockade-the-role-of-pd-1-pd-l-axis-in-lymphoid-mali-peer-reviewed-article-OTT

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