Work

LAG Time in the Era of Immunotherapy—New Molecular Insights Into the Immunosuppression Mechanism of Lymphocyte Activation Gene‐3

Year: 2025

Type: review

Abstract: The immune checkpoint receptor lymphocyte activation gene-3 (LAG3) inhibits T-cell activation and was recently validated as a target for cancer immunotherapy. Despite its emergence as a therapeutic target, a lack of molecular-level insight has obscured our understanding of the LAG3 immunosuppression mechanism. This review highlights a series of breakthroughs that have illuminated fundamental aspects of LAG3 molecular biology. Key discoveries include structural insights into LAG3 interactions with ligands and antibodies, mechanistic studies of LAG3 interference with T-cell receptor (TCR) signaling, and the development of novel therapeutics. A particular focus is placed on structure-function relationships for LAG3-targeting drugs, as it has become apparent that several distinct approaches to LAG3 antagonism are viable. In addition to LAG3 antagonists, agonistic LAG3 antibodies and immunostimulatory LAG3 extracellular domains (ECDs) are discussed in the context of current structural and mechanistic data. Collectively, these findings should provide an updated landscape for the design of optimal LAG3-based therapeutics for cancer and autoimmune diseases.

Source: Immunological Reviews

DOI: 10.1111/imr.70002

Author: Vincent C. Luca

Institution: Moffitt Cancer Center

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Rita Allen Foundation, Florida Department of Health, National Institute of General Medical Sciences