PD-1-PD-L1 immune-checkpoint blockade in B-cell lymphomas.
Cancer cells can escape T-cell-mediated cellular cytotoxicity by exploiting the inhibitory programmed cell-death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) immune checkpoint. Indeed, therapeutic antibodies that block the PD-1-PD-L1 axis induce durable clinical responses against a growing list of solid tumours. B-cell lymphomas also leverage this checkpoint to escape immune recognition, although the outcomes of PD-1-PD-L1 blockade, and the correlations between PD-L1 expression and treatment responses, are less-well elucidated in these diseases than in solid cancers. Nevertheless, in patients with Hodgkin lymphoma, amplification of the gene encoding PD-L1 is commonly associated with increased expression of this protein on Reed-Sternberg cells. Correspondingly, PD-1 blockade with nivolumab has been demonstrated to result in response rates as high as 87% in unselected patients with relapsed and/or refractory Hodgkin lymphoma, leading to the FDA approval of nivolumab for this indication in May 2016. The PD-1/PD-L1 axis is probably also important for immune evasion of B-cell lymphomas with a viral aetiology, including those associated with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV). This Review is focused on the role of PD-1-PD-L1 blockade in unleashing host antitumour immune responses against various B-cell lymphomas, and summarizes the clinical studies of this approach performed to date.
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Drive, La Jolla, California 92093, USA.
Aaron
A
Goodman
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Drive, La Jolla, California 92093, USA.
Sandip P
SP
Patel
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Drive, La Jolla, California 92093, USA.
Razelle
R
Kurzrock
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology; D002986:Clinical Trials as Topic; D006689:Hodgkin Disease / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology*; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000276:immunology; D008479:Mediastinal Neoplasms / Q000276:immunology / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape / Q000276:immunology*
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D061026:Programmed Cell Death 1 Receptor