期刊
CELL
卷 176, 期 1-2, 页码 334-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2018.11.010
关键词
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资金
- NIH from Boehringer Ingelheim [P30 CA16359, P50 CA196530]
- Instituto de Salud Carlos III, Fondo de Investigation Sanitaria (Spain)
- NCI Comprehensive Cancer Center Support CORE [P30 CA047904]
- United Technologies Corporation
- NIH [P01 AI108545]
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.
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