Immune checkpoint blockade in lymphoid malignancies

FEBS J. 2016 Jun;283(12):2233-44. doi: 10.1111/febs.13668. Epub 2016 Feb 22.

Abstract

Malignant cells may subvert and escape endogenous host immune surveillance by up-regulation of immune inhibitory signals known as immune checkpoints. These checkpoints are important therapeutic targets, and antibodies that block checkpoint signaling have shown remarkable efficacy in some solid tumors as well as in some refractory hematologic malignancies. In hematologic cancers, the mechanism of these checkpoints is complex, as the tumor and immune system are one and the same. In this review, we evaluate the biology of checkpoint inhibition, review the current data on its efficacy in lymphoid tumors, and explore uncertainties in the field, including those involving the precise mechanisms of action, the appropriate timing of therapy, and the differences in response rate between lymphoid tumor types.

Keywords: CTLA4; Hodgkin lymphoma; PD-1; biology; immune checkpoint; immunotherapy; myeloma; non-Hodgkin lymphoma; therapy.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / immunology
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / immunology*
  • Hematologic Neoplasms / classification
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunotherapy
  • Lymphoma / classification
  • Lymphoma / genetics
  • Lymphoma / immunology
  • Lymphoma / therapy*
  • Molecular Targeted Therapy*
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor