Blocking tumor escape in hematologic malignancies: the anti-PD-1 strategy

Blood Rev. 2015 Jan;29(1):25-32. doi: 10.1016/j.blre.2014.09.004. Epub 2014 Sep 16.

Abstract

Immunotherapy remains an important tool for treatment of hematologic malignancies. The Programmed Death-1 (PD-1) immune checkpoint pathway has emerged as a mechanism of tumor evasion from the anti-tumor immune response. The recent development of anti-PD-1 monoclonal antibodies has offered a targeted approach to cancer therapy. Several agents are in various stages of development and have shown clinical responses across a broad spectrum of both solid and hematologic malignancies. The use of anti-PD-1 therapy in hematologic malignancies is limited but has demonstrated clinical responses in relapsed/refractory disease following multiple lines of therapy. PD-1 blockade may reduce relapse rates for patients who fail to obtain a complete remission prior to autologous hematopoietic cell transplant. The role of the PD-1 pathway for tumor escape is reviewed. We explore the use of anti-PD-1 therapy in hematologic malignancies. The proposed mechanism of PD-1 blockade as a modulator of the innate and acquired immune response is considered. Finally, the challenges of anti-PD-1 therapy and the future direction of investigation in this area are reviewed.

Keywords: Follicular lymphoma; Hematologic malignancies; Hodgkin lymphoma; Monoclonal antibody; Non-Hodgkin lymphoma (NHL); Plasma cell myeloma (PCM); Programmed Death-1 (PD-1).

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / metabolism
  • Humans
  • Immunotherapy
  • Molecular Targeted Therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Tumor Escape / drug effects*
  • Tumor Escape / immunology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Programmed Cell Death 1 Receptor