Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using Multiplex Quantitative Analysis
| Autor: | Jialei Sun, Peixin Huang, Qian-Wen Rao, Jinglin Xia, Mengzhou Guo, Feng Qi, Biwei Yang, Feifei Yuan, Zhiying Zhao, Tingting Fang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
PD-L1
0301 basic medicine Hepatocellular carcinoma lcsh:Medicine Immunofluorescence General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine LAG-3 medicine Cytotoxic T cell Clinical significance FGL1 Gene Multiplex immunofluorescence staining biology medicine.diagnostic_test Chemistry lcsh:R General Medicine Prognosis Ligand (biochemistry) medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Cancer research biology.protein CD8 |
| Zdroj: | Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-13 (2020) |
| DOI: | 10.21203/rs.3.rs-19039/v2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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