LAG3's Enigmatic Mechanism of Action

被引：127
作者：
Graydon, Colin G. [1 ]
Mohideen, Shifa [1 ]
Fowke, Keith R. [1 ,2 ,3 ,4 ]
机构：
[1] Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB, Canada
[2] Univ Nairobi, Dept Med Micobiol, Nairobi, Kenya
[3] Univ Manitoba, Max Rady Coll Med, Dept Community Hlth Sci, Winnipeg, MB, Canada
[4] Partners Hlth & Dev Africa, Nairobi, Kenya
来源：
FRONTIERS IN IMMUNOLOGY | 2021年 / 11卷
基金：
加拿大健康研究院;
关键词：
LAG3; immune checkpoint; immune exhaustion; checkpoint inhibition; mechanism of action; Lymphocyte activation gene-3; immune checkpoint inhibitors; LYMPHOCYTE-ACTIVATION GENE-3; NEGATIVE REGULATORY FUNCTION; T-CELL; TRANSCRIPTION FACTOR; LAG-3; CD223; EXPRESSION; PROTEIN; LIGAND; MOLECULES; PROLIFERATION;
D O I：
10.3389/fimmu.2020.615317
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
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页数：7
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