Lymphocyte-activation gene-3, an important immune checkpoint in cancer

Cancer Sci. 2016 Sep;107(9):1193-7. doi: 10.1111/cas.12986. Epub 2016 Aug 25.

Abstract

Immunotherapy has recently become widely used in lung cancer. Many oncologists are focused on cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1). Immunotherapy targeting the PD-1/PD-L1 checkpoints has shown promising efficacy in non-small cell lung cancer (NSCLC), but questions remain to be answered. Among them is whether the simultaneous inhibition of other checkpoints could improve outcomes. Lymphocyte-activation gene-3 (LAG-3) is another vital checkpoint that may have a synergistic interaction with PD-1/PD-L1. Here we review the LAG-3 function in cancer, clinical trials with agents targeting LAG-3 and the correlation of LAG-3 with other checkpoints.

Keywords: Cancer checkpoints; clinical trial; immunotherapy; lymphocyte-activation gene-3; soluble LAG-3.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • B7-H1 Antigen / metabolism
  • CTLA-4 Antigen / metabolism
  • Disease Susceptibility
  • Drug Discovery
  • Gene Expression
  • Humans
  • Immunomodulation* / genetics
  • Lymphocyte Activation Gene 3 Protein
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism*
  • Programmed Cell Death 1 Receptor / metabolism
  • Signal Transduction / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human
  • soluble LAG-3 protein, human