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PMID: 30603054 Published · ppublish English Journal Article Review

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

Genes & cancer ·Vol. 9 ·No. 5-6 ·2018-05-00 ·Pages 176-189

Long L, Zhang X, Chen F, Pan Q, Phiphatwatchara P, Zeng Y, Chen H

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.

Keywords
cancer immunotherapy immune checkpoint lymphocyte activation gene-3 tumor microenvironment
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Long Long
Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, P. R. China. | Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, P. R. China.
Zhang Xue
Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, P. R. China.
Chen Fuchun
Department of Thoracosurgery, Traditional Chinese Medical Hospital of Wenling, Wenling, Zhejiang, China.
Pan Qi
Department of Thoracosurgery, Traditional Chinese Medical Hospital of Wenling, Wenling, Zhejiang, China.
Phiphatwatchara Pronnaphat
Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, P. R. China.
Zeng Yuyang
Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, P. R. China.
Chen Honglei
Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, P. R. China.
Conflict of Interest

CONFLICT OF INTERESTS The authors declare no conflict of interest.

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Article Info
Journal
Genes & cancer
Abbr.
Genes Cancer
ISSN
1947-6019
DOI
10.18632/genesandcancer.180
Published
2018-05-00
Pages
176-189
Language
English
Region
United States
NLM ID
101516546
PMCID
PMC6305110
External Links
PubMed source DOI: 10.18632/genesandcancer.180 PMC Full Text
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