The Next-Generation Immune Checkpoint LAG-3 and Its Therapeutic Potential in Oncology: Third Time's a Charm

Int J Mol Sci. 2020 Dec 23;22(1):75. doi: 10.3390/ijms22010075.


The blockade of immune checkpoints (ICPs), such as cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed death-1 (PD-1) and its ligand (PD-L1), has propelled the field of immuno-oncology into its current era. Drugs targeting these ICPs have improved clinical outcome in a number of patients with solid and hematological cancers. Nonetheless, some patients have no benefit from these ICP-blocking therapies. This observation has instigated research into alternative pathways that are responsible for the escape of cancer cells from anti-cancer immune responses. From this research, a number of molecules have emerged as promising therapeutic targets, including lymphocyte activating gene-3 (LAG-3), a next-generation ICP. We will review the current knowledge on the biological activity of LAG-3 and linked herewith its expression on activated immune cells. Moreover, we will discuss the prognostic value of LAG-3 and how LAG-3 expression in tumors can be monitored, which is an aspect that is of utmost importance, as the blockade of LAG-3 is actively pursued in clinical trials.

Keywords: LAG-3; cancer; diagnosis; immune checkpoint; immunotherapy; oncology.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lymphocyte Activation Gene 3 Protein
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy
  • Neoplasms / immunology*


  • Antigens, CD
  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human