LAG-3 as the third checkpoint inhibitor

  • Nat Immunol. 2023 Sep;24(9):1415-1422. doi: 10.1038/s41590-023-01569-z.
Vaishali Aggarwal  1  2 ,  Creg J Workman  1  2 ,  Dario A A Vignali  3  4  5
Affiliations
  • 1. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • 2. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
  • 3. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. [email protected].
  • 4. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. [email protected].
  • 5. Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. [email protected].
PMID: 37488429 DOI: 10.1038/s41590-023-01569-z
Abstract

Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that is highly expressed by exhausted T cells. LAG-3 is a promising immunotherapeutic target, with more than 20 LAG-3-targeting therapeutics in clinical trials and a fixed-dose combination of anti-LAG-3 and anti-PD-1 now approved to treat unresectable or metastatic melanoma. Although LAG-3 is widely recognized as a potent inhibitory receptor, important questions regarding its biology and mechanism of action remain. In this Perspective, we focus on gaps in the understanding of LAG-3 biology and discuss the five biggest topics of current debate and focus regarding LAG-3, including its ligands, signaling and mechanism of action, its cell-specific functions, its importance in different disease settings, and the development of novel therapeutics.