LAG-3: from molecular functions to clinical applications
To prevent the destruction of tissues owing to excessive and/or inappropriate immune responses, immune cells are under strict check by various regulatory mechanisms at multiple points. Inhibitory coreceptors, including programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), ser...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001014.full |
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| author | Takumi Maruhashi Daisuke Sugiura Il-mi Okazaki Taku Okazaki |
| author_facet | Takumi Maruhashi Daisuke Sugiura Il-mi Okazaki Taku Okazaki |
| author_sort | Takumi Maruhashi |
| collection | DOAJ |
| description | To prevent the destruction of tissues owing to excessive and/or inappropriate immune responses, immune cells are under strict check by various regulatory mechanisms at multiple points. Inhibitory coreceptors, including programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), serve as critical checkpoints in restricting immune responses against self-tissues and tumor cells. Immune checkpoint inhibitors that block PD-1 and CTLA-4 pathways significantly improved the outcomes of patients with diverse cancer types and have revolutionized cancer treatment. However, response rates to such therapies are rather limited, and immune-related adverse events are also observed in a substantial patient population, leading to the urgent need for novel therapeutics with higher efficacy and lower toxicity. In addition to PD-1 and CTLA-4, a variety of stimulatory and inhibitory coreceptors are involved in the regulation of T cell activation. Such coreceptors are listed as potential drug targets, and the competition to develop novel immunotherapies targeting these coreceptors has been very fierce. Among such coreceptors, lymphocyte activation gene-3 (LAG-3) is expected as the foremost target next to PD-1 in the development of cancer therapy, and multiple clinical trials testing the efficacy of LAG-3-targeted therapy are underway. LAG-3 is a type I transmembrane protein with structural similarities to CD4. Accumulating evidence indicates that LAG-3 is an inhibitory coreceptor and plays pivotal roles in autoimmunity, tumor immunity, and anti-infection immunity. In this review, we summarize the current understanding of LAG-3, ranging from its discovery to clinical application. |
| format | Article |
| id | doaj-art-950de31b1ac94cbfa1aec9f714d117d7 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-950de31b1ac94cbfa1aec9f714d117d72025-08-20T02:13:19ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001014LAG-3: from molecular functions to clinical applicationsTakumi Maruhashi0Daisuke Sugiura1Il-mi Okazaki2Taku Okazaki3Laboratory of Molecular Immunology, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, JapanLaboratory of Molecular Immunology, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, JapanLaboratory of Molecular Immunology, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, JapanLaboratory of Molecular Immunology, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, JapanTo prevent the destruction of tissues owing to excessive and/or inappropriate immune responses, immune cells are under strict check by various regulatory mechanisms at multiple points. Inhibitory coreceptors, including programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), serve as critical checkpoints in restricting immune responses against self-tissues and tumor cells. Immune checkpoint inhibitors that block PD-1 and CTLA-4 pathways significantly improved the outcomes of patients with diverse cancer types and have revolutionized cancer treatment. However, response rates to such therapies are rather limited, and immune-related adverse events are also observed in a substantial patient population, leading to the urgent need for novel therapeutics with higher efficacy and lower toxicity. In addition to PD-1 and CTLA-4, a variety of stimulatory and inhibitory coreceptors are involved in the regulation of T cell activation. Such coreceptors are listed as potential drug targets, and the competition to develop novel immunotherapies targeting these coreceptors has been very fierce. Among such coreceptors, lymphocyte activation gene-3 (LAG-3) is expected as the foremost target next to PD-1 in the development of cancer therapy, and multiple clinical trials testing the efficacy of LAG-3-targeted therapy are underway. LAG-3 is a type I transmembrane protein with structural similarities to CD4. Accumulating evidence indicates that LAG-3 is an inhibitory coreceptor and plays pivotal roles in autoimmunity, tumor immunity, and anti-infection immunity. In this review, we summarize the current understanding of LAG-3, ranging from its discovery to clinical application.https://jitc.bmj.com/content/8/2/e001014.full |
| spellingShingle | Takumi Maruhashi Daisuke Sugiura Il-mi Okazaki Taku Okazaki LAG-3: from molecular functions to clinical applications Journal for ImmunoTherapy of Cancer |
| title | LAG-3: from molecular functions to clinical applications |
| title_full | LAG-3: from molecular functions to clinical applications |
| title_fullStr | LAG-3: from molecular functions to clinical applications |
| title_full_unstemmed | LAG-3: from molecular functions to clinical applications |
| title_short | LAG-3: from molecular functions to clinical applications |
| title_sort | lag 3 from molecular functions to clinical applications |
| url | https://jitc.bmj.com/content/8/2/e001014.full |
| work_keys_str_mv | AT takumimaruhashi lag3frommolecularfunctionstoclinicalapplications AT daisukesugiura lag3frommolecularfunctionstoclinicalapplications AT ilmiokazaki lag3frommolecularfunctionstoclinicalapplications AT takuokazaki lag3frommolecularfunctionstoclinicalapplications |