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 considered a next-generation target in cancer immunotherapy, right next to PD-1 and CTLA-4. Unlike PD-1 and CTLA-4, the exact mechanisms of action of LAG-3 remain poorly understood. Indeed, PD-1/LAG-3 co-expression is a marker for exhausted T lymphocytes infiltrating tumors. This constitutes a high-risk signature, but also a clinical factor associated to overall survival. The lack of understanding of LAG-3 functions is partly caused by the presence of non-conventional signaling motifs in its intracellular domain, different from others present in classical immune checkpoints. Here we summarize the current understanding on LAG-3 and its role in response and resistance to cancer therapy, from its mechanisms of action to clinical applications (Chocarro de Erauso L et al, Front. Pharmacol. 2020; Zuazo et al, Font Immunol 2020; Bocanegra et al, Int J Mol Sci 2020; Hernández et al, Int J Mol Sci 2020; Arasanz et al, Cancers 2020; Chocarro et al, Int J Mol Sci 2021).
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Role of the next-generation immune checkpoint LAG-3 in response and resistance to cancer immunotherapy
Published: 23 March 2022 by MDPI in MOL2NET'22, Conference on Molecular, Biomed., Comput. & Network Science and Engineering, 8th ed. congress CHEMBIO.ORG-08: Org. Chem., Med. Chem., Mol. Biol., & Pharm. Industry Congress, Paris, France-Galveston, USA, 2022.
Keywords: LAG-3, PD-1, immunotherapy, immune checkpoint