Immune Checkpoints as a Target for Colorectal Cancer Treatment

Int J Mol Sci. 2017 Jun 21;18(6):1324. doi: 10.3390/ijms18061324.

Abstract

Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies. We present an updated review of the biological background and clinical development of immune checkpoint inhibitors in colorectal cancer (CRC). Early trial results on PD1 and PD-L1 blockade appear promising, especially in CRC patients with microsatellite instability (MSI). Clinical trials are ongoing to confirm these preliminary results, evaluate combination strategies and identify biomarkers to predict which patients are most likely to benefit from, or show resistance to, the effects of checkpoint inhibition.

Keywords: colorectal cancer; immune checkpoint inhibitors; microsatellite instability (MSI); programmed cell death protein ligand 1 (PD-L1); programmed death-1 receptor (PD1).

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / immunology
  • Colon / drug effects
  • Colon / immunology
  • Colon / metabolism
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • Drug Discovery
  • Humans
  • Immunity / drug effects*
  • Microsatellite Instability
  • Molecular Targeted Therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Rectum / drug effects
  • Rectum / immunology
  • Rectum / metabolism

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor