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

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 correlatio...

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Autores principales: Guo, Mengzhou, Yuan, Feifei, Qi, Feng, Sun, Jialei, Rao, Qianwen, Zhao, Zhiying, Huang, Peixin, Fang, Tingting, Yang, Biwei, Xia, Jinglin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409704/
https://www.ncbi.nlm.nih.gov/pubmed/32762721
http://dx.doi.org/10.1186/s12967-020-02469-8
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author Guo, Mengzhou
Yuan, Feifei
Qi, Feng
Sun, Jialei
Rao, Qianwen
Zhao, Zhiying
Huang, Peixin
Fang, Tingting
Yang, Biwei
Xia, Jinglin
author_facet Guo, Mengzhou
Yuan, Feifei
Qi, Feng
Sun, Jialei
Rao, Qianwen
Zhao, Zhiying
Huang, Peixin
Fang, Tingting
Yang, Biwei
Xia, Jinglin
author_sort Guo, Mengzhou
collection PubMed
description 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.
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spelling pubmed-74097042020-08-10 Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8(+)T cells in hepatocellular carcinoma using multiplex quantitative analysis Guo, Mengzhou Yuan, Feifei Qi, Feng Sun, Jialei Rao, Qianwen Zhao, Zhiying Huang, Peixin Fang, Tingting Yang, Biwei Xia, Jinglin J Transl Med Research 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. BioMed Central 2020-08-06 /pmc/articles/PMC7409704/ /pubmed/32762721 http://dx.doi.org/10.1186/s12967-020-02469-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Guo, Mengzhou
Yuan, Feifei
Qi, Feng
Sun, Jialei
Rao, Qianwen
Zhao, Zhiying
Huang, Peixin
Fang, Tingting
Yang, Biwei
Xia, Jinglin
Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8(+)T cells in hepatocellular carcinoma using multiplex quantitative analysis
title Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8(+)T cells in hepatocellular carcinoma using multiplex quantitative analysis
title_full Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8(+)T cells in hepatocellular carcinoma using multiplex quantitative analysis
title_fullStr Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8(+)T cells in hepatocellular carcinoma using multiplex quantitative analysis
title_full_unstemmed Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8(+)T cells in hepatocellular carcinoma using multiplex quantitative analysis
title_short Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8(+)T cells in hepatocellular carcinoma using multiplex quantitative analysis
title_sort expression and clinical significance of lag-3, fgl1, pd-l1 and cd8(+)t cells in hepatocellular carcinoma using multiplex quantitative analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409704/
https://www.ncbi.nlm.nih.gov/pubmed/32762721
http://dx.doi.org/10.1186/s12967-020-02469-8
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