Understanding LAG-3 Signaling

Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule comparable to PD-1 and CTLA-4...

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Bibliographic Details
Authors: Chocarro de Erauso, Luisa, Blanco, Ester, Zuazo Ibarra, Miren, Arasanz Esteban, Hugo, Bocanegra Gondán, Ana Isabel, Fernández Rubio, Leticia, Morente Sancho, Pilar, Fernández Hinojal, Gonzalo, Echaide Górriz, Míriam, Garnica, Maider, Ramos, Pablo, Vera García, Ruth, Kochan, Grazyna, Escors Murugarren, David
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Universidad Pública de Navarra
Repository:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/41811
Online Access:https://hdl.handle.net/2454/41811
Access Level:Open access
Keyword:LAG-3
Immune checkpoint
Cancer signaling
Immunotherapy
Targeted therapy
Description
Summary:Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule comparable to PD-1 and CTLA-4 and a potential target for enhancing anti-cancer immune responses. LAG-3 is the third inhibitory receptor to be exploited in human anti-cancer immunotherapies, and it is considered a potential next-generation cancer immunotherapy target in human therapy, right next to PD-1 and CTLA-4. Unlike PD-1 and CTLA-4, the exact mechanisms of action of LAG-3 and its relationship with other immune checkpoint molecules remain poorly understood. This is partly caused by the presence of non-conventional signaling motifs in its intracellular domain that are different from other conventional immunoregulatory signaling motifs but with similar inhibitory activities. Here we summarize the current understanding of LAG-3 signaling and its role in LAG-3 functions, from its mechanisms of action to clinical applications.