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Cited by 459

The DOI matches its Crossref record; 116 of the 116 references it cites were found in a registry or an index.

LAG-3: from molecular functions to clinical applications

Open access
Maruhashi, Takumi, Sugiura, Daisuke, Okazaki, Il-mi, Okazaki, Taku·2020·Journal for ImmunoTherapy of Cancer

Abstract

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.

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Metadata

Authors
Maruhashi, T., Sugiura, D., Okazaki, I.-M., & Okazaki, T.
Venue
Journal for ImmunoTherapy of Cancer
Publisher
BMJ
Published
2020-09
Volume
8
Issue
2
Pages
e001014
ISSN
2051-1426 (ISSN-L)
OpenAlex
W3085860981
Cited by
459
References
116
FWCI
20.05
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: LAG-3: from molecular functions to clinical applications. https://app.cochat.ai/papers/10.1136/jitc-2020-001014
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Maruhashi, T., Sugiura, D., Okazaki, I.-M., & Okazaki, T. (2020). LAG-3: from molecular functions to clinical applications. Journal for ImmunoTherapy of Cancer. https://doi.org/10.1136/jitc-2020-001014

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