PD-1–PD-L1 immune-checkpoint blockade in B-cell lymphomas

A Goodman, SP Patel, R Kurzrock - Nature reviews Clinical oncology, 2017 - nature.com
A Goodman, SP Patel, R Kurzrock
Nature reviews Clinical oncology, 2017nature.com
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 …
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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