Fig. 5.

TNFα and IL-6 signalling influence response to BRAF/MEK inhibitors. a) Correlation between the MAPK inhibitors dabrafenib and trametinib IC₅₀ values and Hallmark gene sets. Data analysed using Pearson correlation, correlation with p < 0.01 shown and Pearson r coefficient values plotted on the x axis. b) Scatterplots showing correlation of the Hallmark TNFA and IL-6 signalling gene sets with dabrafenib and trametinib IC₅₀ values in melanoma cell lines (n = 13). Undifferentiated melanoma cell lines highlighted in red. Pearson correlation is shown. c) Cell viability plots showing change in dabrafenib and trametinib IC₅₀ values. Cells were pre-treated with IL6 (25 ng/ml) or TNFα (1000 U/ml) for 72 h, followed by treatment with increasing concentrations of dabrafenib + trametinib (DT, at 10:1 ratio) ± IL6 (25 ng/ml, green) or TNFα (1000 U/ml, blue) in the SMU11-0270 and SMU11-0376 M4 melanocytic and SMU17-0132 undifferentiated cell lines compared to control (0.1% BSA, black). Area under curve (AUC) analysis was performed and the AUC values were used for statistical comparison (unpaired t-test, IL6 or TNFα compared to control treatment, dabrafenib and trametinib IC₅₀ values and p values shown). At least three biological replicates were performed for each cell line.