Understanding LAG-3 Signaling |
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| Authors: | Luisa Chocarro Ester Blanco Miren Zuazo Hugo Arasanz Ana Bocanegra Leticia Fernndez-Rubio Pilar Morente Gonzalo Fernndez-Hinojal Miriam Echaide Maider Garnica Pablo Ramos Ruth Vera Grazyna Kochan David Escors |
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| Affiliation: | 1.Oncoimmunology Group, Navarrabiomed-Public University of Navarre, IdISNA, 31008 Pamplona, Navarra, Spain; (L.C.); (E.B.); (M.Z.); (H.A.); (A.B.); (L.F.-R.); (P.M.); (G.F.-H.); (M.E.); (M.G.); (P.R.);2.Department of Medical Oncology, Complejo Hospitalario de Navarra CHN-IdISNA, 31008 Pamplona, Navarra, Spain; |
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| Abstract: | 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. |
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| Keywords: | LAG-3 immune checkpoint cancer signaling immunotherapy targeted therapy |
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