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. 2021 Dec 15;12:797261. doi: 10.3389/fimmu.2021.797261

Figure 1.

Figure 1

Dynamics of regulatory network coupling EMT with PD-L1. (A) Regulatory network (GRN) capturing the interplay of EMT regulators coupled with PD-L1. Blue arrows stand for activation links, red hammers for inhibitory links. (B) Density histogram of EM Score fitted with kernel density estimate showing a trimodal distribution. Red lines show the partition between phenotypes: Epithelial, Hybrid, and Mesenchymal. (C) Scatter plot of PD-L1 expression and EM score. Horizontal red line shows the partition between PDL1 expression level being high vs. low. Vertical red lines show the partition between phenotypes: Epithelial, Hybrid, and Mesenchymal based on EM score. Spearman’s correlation coefficient (ρ) and corresponding p-value (p-val) have been reported. (D) Bar plot representing the conditional probability of a phenotype being PD-L1 high given that it belongs to a given EMT phenotype. Error bars denote standard deviation calculated on three independent simulations. (E) Scatter plot showing correlation between PD-L1 levels and the Hallmark EMT signature in cell lines from CCLE. Spearman’s correlation coefficient (ρ) and corresponding p-value (p-val) are reported (left panel). Splitting CCLE cell lines reveals tissues that show a strong significant correlation (ρ > 0.3 and p-val < 0.01) (right panel). (F) Activity levels of Hallmark EMT and PD-L1 expression levels in 3 breast cancer cell lines (GSE75168). (G) Activity/Expression levels of Hallmark EMT and PD-L1 levels in MCF10A breast cancer cells treated with or without growth factors (GSE85857). (H) Activity/Expression levels of Hallmark EMT and PD-L1 levels in two prostate cancer sub-lines of PC3 with different EMT status (GSE24868). (I) Heatmap showing the Spearman’s correlation coefficients between the different EM metrics and EMT associated genes and PD-L1 levels across 32 different cancer types in TCGA. * denotes a statistically significant difference (p-val < 0.05) between the represented groups assessed by a two-tailed Students t-test assuming unequal variances.