Key Points
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A large percentage of patients with classic Hodgkin lymphoma (CHL), primary mediastinal B-cell lymphoma (PMBCL), primary testicular lymphoma, and primary central nervous system lymphoma have copy-number alterations and/or translocations involving the 9p24.1 locus
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The 9p24.1 locus contains the genes encoding programmed cell death 1 ligands 1 and 2 (PD-L1 and PD-L2), and JAK2; lymphoma-associated aberrations in this locus result in increased expression of these proteins
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PD-L1 and/or PD-L2 induce immunosuppressive signalling via programmed cell-death protein 1 (PD-1); blockade of PD-1 with nivolumab results in response rates as high as 87% in patients with relapsed/refractory CHL
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Nivolumab is currently approved by the FDA for the treatment of relapsed/refractory CHL, and many trials are underway to evaluate PD-1–PD-L1 blockade in patients with B-cell lymphomas
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The PD-1–PD-L1 axis is probably important for immune evasion of B-cell lymphomas with a viral aetiology, specifically Epstein–Barr virus (EBV)-associated and human immunodeficiency virus (HIV)-associated lymphomas
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PD-1 inhibition in diffuse large-B-cell lymphoma might be most effective when directed at specific disease subtypes, including PMBCL, T-cell/histiocyte-rich large-B-cell lymphoma, and EBV-positive disease
Abstract
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.
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The work of the authors is funded, in part, by the Joan and Irwin Jacobs Philanthropic Fund.
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A.G. researched the data for the article and wrote the manuscript. A.G. and R.K. provided substantial contributions to discussions of the content. All authors reviewed and/or edited the manuscript before submission.
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A.G. has received fellowship funding from Pfizer. S.P.P. has received research funding from Amgen, MedImmune, Pfizer, and Xcovery; consulting fees from Lilly; and speaking fees from Boehringer Ingelheim. R.K. has received research funds from Foundation Medicine, Genentech, Guardant, Merck Serono, Pfizer, and Sequenom; consultant fees from Sequenom; and has an ownership interest in CureMatch and Novena.
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Goodman, A., Patel, S. & Kurzrock, R. PD-1–PD-L1 immune-checkpoint blockade in B-cell lymphomas. Nat Rev Clin Oncol 14, 203–220 (2017). https://doi.org/10.1038/nrclinonc.2016.168
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DOI: https://doi.org/10.1038/nrclinonc.2016.168
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