Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy

Cancer Cell. 2015 Apr 13;27(4):450-61. doi: 10.1016/j.ccell.2015.03.001. Epub 2015 Apr 6.

Abstract

The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands. These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during anti-microbial immune responses, can be co-opted by cancer to evade immune destruction. Drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, anti-PD-L1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions. The complex biology of immune checkpoint pathways still contains many mysteries, and the full activity spectrum of checkpoint-blocking drugs, used alone or in combination, is currently the subject of intense study.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • CD28 Antigens / antagonists & inhibitors
  • CD28 Antigens / immunology
  • CD28 Antigens / physiology
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / physiology
  • Humans
  • Immunotherapy
  • Models, Immunological*
  • Neoplasms / immunology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / physiology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CD28 Antigens
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor