Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3.
Animals
Antigens, CD
/ immunology
Cell Line
Fibrinogen
/ immunology
Genes, MHC Class II
/ genetics
Histocompatibility Antigens Class II
/ genetics
Humans
Immunotherapy
Ligands
Liver
/ metabolism
Lymphocyte Activation
/ immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasm Proteins
/ genetics
Neoplasms
/ immunology
T-Lymphocytes, Cytotoxic
/ immunology
Lymphocyte Activation Gene 3 Protein
FGL1
LAG-3
cancer
immunology
immunotherapy
tumor immune-evasion mechanism
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
10 01 2019
10 01 2019
Historique:
received:
28
06
2018
revised:
13
10
2018
accepted:
09
11
2018
pubmed:
26
12
2018
medline:
14
11
2019
entrez:
25
12
2018
Statut:
ppublish
Résumé
Lymphocyte-activation gene 3 (LAG-3) is an immune inhibitory receptor, with major histocompatibility complex class II (MHC-II) as a canonical ligand. However, it remains controversial whether MHC-II is solely responsible for the inhibitory function of LAG-3. Here, we demonstrate that fibrinogen-like protein 1 (FGL1), a liver-secreted protein, is a major LAG-3 functional ligand independent from MHC-II. FGL1 inhibits antigen-specific T cell activation, and ablation of FGL1 in mice promotes T cell immunity. Blockade of the FGL1-LAG-3 interaction by monoclonal antibodies stimulates tumor immunity and is therapeutic against established mouse tumors in a receptor-ligand inter-dependent manner. FGL1 is highly produced by human cancer cells, and elevated FGL1 in the plasma of cancer patients is associated with a poor prognosis and resistance to anti-PD-1/B7-H1 therapy. Our findings reveal an immune evasion mechanism and have implications for the design of cancer immunotherapy.
Identifiants
pubmed: 30580966
pii: S0092-8674(18)31502-2
doi: 10.1016/j.cell.2018.11.010
pmc: PMC6365968
mid: NIHMS1516788
pii:
doi:
Substances chimiques
Antigens, CD
0
FGL1 protein, human
0
Histocompatibility Antigens Class II
0
Ligands
0
Neoplasm Proteins
0
Fibrinogen
9001-32-5
Lymphocyte Activation Gene 3 Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
334-347.e12Subventions
Organisme : NIAID NIH HHS
ID : P01 AI108545
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016359
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA047904
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA196530
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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