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

Nat Rev Clin Oncol. 2017 Apr;14(4):203-220. doi: 10.1038/nrclinonc.2016.168. Epub 2016 Nov 2.

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.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology*
  • B7-H1 Antigen / metabolism
  • CTLA-4 Antigen / immunology
  • Clinical Trials as Topic
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / immunology
  • Humans
  • Immunity, Cellular / immunology
  • Immunotherapy / methods
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, Follicular / drug therapy
  • Lymphoma, Follicular / immunology
  • Mediastinal Neoplasms / immunology
  • Mediastinal Neoplasms / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology*
  • Programmed Cell Death 1 Receptor / metabolism
  • Tumor Escape / immunology*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Programmed Cell Death 1 Receptor