Checkpoint inhibition: Programmed cell death 1 and programmed cell death 1 ligand inhibitors in Hodgkin lymphoma

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by a reactive immune infiltrate surrounding relatively few malignant cells. In this scenario, active immune evasion seems to play a central role in allowing tumor progression. Immune checkpoint inhibitor pathways are normal mechanisms of T-cell regulation that suppress immune effector function following an antigenic challenge. Hodgkin lymphoma cells are able to escape immune surveillance by co-opting these mechanisms. The programmed cell death 1 (PD-1) pathway in particular is exploited in HL as the malignant Hodgkin and Reed-Sternberg cells express on their surface cognate ligands (PD-L1/L2) for the PD-1 receptor and thereby dampen the T-cell-mediated antitumoral response. Monoclonal antibodies that interact with and disrupt the PD-1:PD-L1/L2 axis have now been developed and tested in early-phase clinical trials in patients with advanced HL with encouraging results. The remarkable clinical activity of PD-1 inhibitors in HL highlights the importance of immune checkpoint pathways as therapeutic targets in HL. In this review, we discuss the rationale for targeting PD-1 and PD-L1 in the treatment of HL. We will evaluate the published clinical data on the different agents and highlight the safety profile of this class of agents. We discuss the available evidence on the use of biomarkers as predictors of response to checkpoint blockade and summarize the areas under active investigation in the use of PD-1/PD-L1 inhibitors for the treatment of HL.

Original languageEnglish (US)
Pages (from-to)17-22
Number of pages6
JournalCancer Journal (United States)
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Checkpoint inhibitors
  • Hodgkin lymphoma
  • PD-1
  • PD-L1
  • immune-related adverse events
  • immunotherapy
  • ipilimumab
  • nivolumab
  • pembrolizumab
  • pidilizumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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