Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using Multiplex Quantitative Analysis
Background FGL1-LAG-3 pathway is a promising immunotherapeutic target and has synergistic effect with PD-1/PD-L1. However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unkonwn. Method The distributions, associations, and clinical significances of LAG-3, FGL1, PD-L1 and CD8 protein expression in 143 HCC patients were assessed by multiplex immunofluorescence. Results We found FGL1 and LAG-3 densities were elevated while
... ere 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 asscociation 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. Paitents with positive PD-L1 expression on tumor cells (PD-L1TC + ) tended to have a improved survival than that with negative PD-L1 expression on tumor cells (PD-L1TC - ). Futhermore, PD-L1TC - in combination with high densities of LAG-3 + cells showed the worst prognosis, and PD-L1TC + 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. Levels of LAG-3 + cells in combination with PD-L1 status on tumor cells have potential to identify patients who may benefit from immune checkpoints blockade combination strategies.