NDLI: Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using multiplex quantitative analysis

Content Provider	Springer Nature : BioMed Central
Author	Guo, Mengzhou Yuan, Feifei Qi, Feng Sun, Jialei Rao, Qianwen Zhao, Zhiying Huang, Peixin Fang, Tingting Yang, Biwei Xia, Jinglin
Abstract	Background Fibrinogen-like protein 1 (FGL1)—Lymphocyte activating gene 3 (LAG-3) pathway is a promising immunotherapeutic target and has synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1). However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unknown. Methods The levels of LAG-3, FGL1, PD-L1 and cytotoxic T (CD8+T) cells in 143 HCC patients were assessed by multiplex immunofluorescence. Associations between the marker’s expression and clinical significances were studied. Results We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3+cells but not PD-L1. CD8+ T cells densities had positive correlation with PD-L1 levels and negative association with FGL1 expression. Elevated densities of LAG-3+cells and low levels of CD8+ T cells were correlated with poor disease outcome. Moreover, LAG-3+cells deteriorated patient stratification based on the abundance of CD8+ T cells. Patients with positive PD-L1 expression on tumor cells (PD-L1 TC+) tended to have an improved survival than that with negative PD-L1 expression on tumor cells (PD-L1 TC−). Furthermore, PD-L1 TC− in combination with high densities of LAG-3+cells showed the worst prognosis, and PD-L1 TC+ patients with low densities of LAG-3+cells had the best prognosis. Conclusions LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3+cells and CD8+ T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively.
Related Links	https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-020-02469-8.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	14795876
DOI	10.1186/s12967-020-02469-8
Journal	Journal of Translational Medicine
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2020-08-06
Access Restriction	Open
Subject Keyword	Biomedicine Medicine Public Health LAG-3 FGL1 PD-L1 Hepatocellular carcinoma Prognosis Multiplex immunofluorescence staining Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology Medicine
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	6.3/2023

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