Checkpoint blockade for cancer therapy: revitalizing a suppressed immune system

Trends Mol Med. 2015 Aug;21(8):482-91. doi: 10.1016/j.molmed.2015.05.005. Epub 2015 Jun 16.

Abstract

Immune checkpoint receptors are crucial molecules for fine-tuning immune responses. Checkpoint signaling dampens T cell activation to avoid autoimmunity and the destructive effects of an excessive inflammatory response. It is well established that tumors use several mechanisms to avoid elimination by the immune system, and one involves hijacking these checkpoint pathways. Checkpoint blockade therapy utilizes monoclonal antibodies to release the brakes from suppressed T cells, allowing them to be activated and recover their antitumor activity. This therapeutic approach has revolutionized cancer immunotherapy, and extraordinary increases in overall survival were noted, first with anti-CTLA-4 (cytotoxic T lymphocyte-associated protein 4) and subsequently with anti-PD-1 (programmed cell death receptor-1) in melanoma and other malignancies.

Keywords: CTLA-4; MDSCs; PD-1; cancer immunotherapy; checkpoint blockade.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / metabolism
  • Cancer Vaccines
  • Combined Modality Therapy
  • Humans
  • Immunosuppression
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Immunotherapy
  • Ligands
  • Molecular Targeted Therapy
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / metabolism
  • Radiotherapy
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • CTLA-4 Antigen
  • Cancer Vaccines
  • Immunosuppressive Agents
  • Ligands
  • Programmed Cell Death 1 Receptor