LAG3's Enigmatic Mechanism of Action.
Colin G Graydon, Shifa Mohideen, Keith R Fowke
Journal: Frontiers in immunology
2021;11():615317
PMID: 33488626
Abstract
["LAG3 is an important immune checkpoint with relevance in cancer, infectious disease and autoimmunity. However, despite LAG3's role in immune exhaustion and the great potential of LAG3 inhibition as treatment, much remains unknown about its biology, particularly its mechanism of action. This review describes the knowns, unknowns and controversies surrounding LAG3. This includes examination of how LAG3 is regulated transcriptionally and post-translationally by endocytosis and proteolytic cleavage. We also discuss the interactions of LAG3 with its ligands and the purpose thereof. Finally, we review LAG3's mechanism of action, including the roles of LAG3 intracellular motifs and the lack of a role for CD4 competition. Overall, understanding the biology of LAG3 can provide greater insight on LAG3 function, which may broaden the appreciation for LAG3's role in disease and potentially aid in the development of targeted therapies.",{"copyright":"Copyright \u00a9 2021 Graydon, Mohideen and Fowke."}]
Address:
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.; Department of Medical Micobiology, University of Nairobi, Nairobi, Kenya.; Department of Community Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.; Partners for Health and Development in Africa, Nairobi, Kenya.
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MeSH Terms:
ADAM10 Protein,
ADAM17 Protein,
Amino Acid Motifs,
Antigens, CD,
Clinical Trials as Topic,
Dendritic Cells,
Endocytosis,
Gene Expression Regulation,
Humans,
Immune Checkpoint Inhibitors,
Immune Checkpoint Proteins,
Ligands,
Lymphocyte Subsets,
Molecular Targeted Therapy,
Neoplasms,
Neurons,
Protein Biosynthesis,
Protein Processing, Post-Translational,
Receptors, Antigen, T-Cell,
Transcription, Genetic,
Lymphocyte Activation Gene 3 Protein
