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Cited by 386Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy

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Long, Long, Zhang, Xue, Chen, Fuchun, Pan, Qi, Phiphatwatchara, Pronnaphat, Zeng, Yuyang, Chen, Honglei·2018·Genes & Cancer
DOI 10.18632/genesandcancer.180PMC PMC6305110
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Abstract

Cancer immunotherapy and tumor microenvironment have been at the forefront of research over the past decades. Targeting immune checkpoints especially programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) has made a breakthrough in treating advanced malignancies. However, the low response rate brings a daunting challenge, changing the focus to dig deeply into the tumor microenvironment for alternative therapeutic targets. Strikingly, the inhibitory immune checkpoint lymphocyte activation gene-3 (LAG-3) holds considerable potential. LAG-3 suppresses T cells activation and cytokines secretion, thereby ensuring immune homeostasis. It exerts differential inhibitory impacts on various types of lymphocytes and shows a remarkable synergy with PD-1 to inhibit immune responses. Targeting LAG-3 immunotherapy is moving forward in active clinical trials, and combination immunotherapy of anti-LAG-3 and anti-PD-1 has shown exciting efficacy in fighting PD-1 resistance. Herein, we shed light on the significance of LAG-3 in the tumor microenvironment, highlight its role to regulate different lymphocytes, interplay with other immune checkpoints especially PD-1, and emphasize new advances in LAG-3-targeted immunotherapy.

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Sorted by citations

Authors
Long, L., Zhang, X., Chen, F., Pan, Q., Phiphatwatchara, P., Zeng, Y., & Chen, H.
Affiliations
  • Wuhan University (CN)
  • Department of Thoracosurgery, Traditional Chinese Medical Hospital of Wenling, Wenling, Zhejiang, China
Corresponding author
Chen, Honglei
ORCID
Venue
Genes & Cancer
Publisher
Impact Journals, LLC
Published
2018-09-23
Volume
9
Issue
5-6
Pages
176-189
ISSN
  • 1947-6019 (ISSN-L)
  • 1947-6027
DOI
10.18632/genesandcancer.180
PMC
PMC6305110
OpenAlex
W2982786601
Cited by
386
References
4
Citations by year
2026: 25 · 2025: 37 · 2024: 44 · 2023: 58 · 2022: 59 · 2021: 62 · 2020: 76 · 2019: 25
FWCI
4.25
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Genes & Cancer (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
LAG-3, immune checkpoint, tumor microenvironment, cancer immunotherapy, PD-1/PD-L1, anti-PD-1 resistance, combination immunotherapy, anti-LAG-3 antibody, T cell activation, lymphocyte regulation, immune homeostasis

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