دورية أكاديمية
The immune checkpoint receptor LAG3: Structure, function, and target for cancer immunotherapy.
| العنوان: | The immune checkpoint receptor LAG3: Structure, function, and target for cancer immunotherapy. |
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| المؤلفون: | Mariuzza RA; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, Maryland, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA. Electronic address: rmariuzz@umd.edu., Shahid S; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, Maryland, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA., Karade SS; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, Maryland, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2024 May; Vol. 300 (5), pp. 107241. Date of Electronic Publication: 2024 Mar 30. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Antigens, CD*/immunology , Antigens, CD*/metabolism , Antigens, CD*/chemistry , Immunotherapy*/methods , Lymphocyte Activation Gene 3 Protein*/immunology , Neoplasms*/therapy , Neoplasms*/immunology , Neoplasms*/metabolism, Animals ; Humans ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Antigen, T-Cell/chemistry |
| مستخلص: | Lymphocyte activation gene 3 protein (LAG3) is an immune checkpoint receptor that is highly upregulated on exhausted T cells in the tumor microenvironment. LAG3 transmits inhibitory signals to T cells upon binding to MHC class II and other ligands, rendering T cells dysfunctional. Consequently, LAG3 is a major target for cancer immunotherapy with many anti-LAG3 monoclonal antibodies (mAbs) that block LAG3 inhibitory activity in clinical trials. In this review, we examine the molecular basis for LAG3 function in light of recently determined crystal and cryoEM structures of this inhibitory receptor. We review what is known about LAG3 interactions with MHC class II, its canonical ligand, and the newly discovered ligands FGL1 and the T cell receptor (TCR)-CD3 complex, including current controversies over the relative importance of these ligands. We then address the development and mechanisms of action of anti-LAG3 mAbs in clinical trials for cancer immunotherapy. We discuss new strategies to therapeutically target LAG3 using mAbs that not only block the LAG3-MHC class II interaction, but also LAG3 interactions with FGL1 or TCR-CD3, or that disrupt LAG3 dimerization. Finally, we assess the possibility of developing mAbs that enhance, rather than block, LAG3 inhibitory activity as treatments for autoimmune diseases. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: FGL1; LAG3; MHC; immune checkpoint; structure |
| المشرفين على المادة: | 0 (Antigens, CD) 0 (Lag3 protein, human) 0 (Lymphocyte Activation Gene 3 Protein) 0 (Receptors, Antigen, T-Cell) |
| تواريخ الأحداث: | Date Created: 20240331 Date Completed: 20240529 Latest Revision: 20240605 |
| رمز التحديث: | 20240605 |
| مُعرف محوري في PubMed: | PMC11061240 |
| DOI: | 10.1016/j.jbc.2024.107241 |
| PMID: | 38556085 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2024.107241 |