Fig. 4

Trametinib upregulates IFN-γ-mediated PD-L1 expression through Id1 downregulation in KRAS-mutant LUAD cells. A PD-L1 expression assessed by flow cytometry in KRAS-mutant mouse (upper panel) and human (lower panel) cells lines transduced or not with lentiviral shRNAs targeting Id1 (sh1-Id1 and sh2-Id1 in mice and sh-Id1 in human). B Upper panel: PD-L1 expression assessed by flow cytometry in parental and TR KRAS-mutant mouse (left) and human (right) cells lines. Parental cells were treated with trametinib (TRAM) (100 nM in murine cells and 500 nM in human cells) for 72 h or vehicle (Control). TR-cell lines were cultured in cell media with trametinib (500 nM). Lower panel: PD-L1 expression assessed by flow cytometry in KRAS-mutant mouse (left) and human cells lines (right) transduced with an Id1-flag cDNA expressing vector (Id1-flag) or a GFP cDNA expressing vector (Control). Cells were treated with trametinib (TRAM) (100 nM in murine cells and 500 nM in human cells) for 72 h or vehicle (Control). Mouse cells were incubated or not with murine IFN-γ (1500 U/ml) for 24 h and human cells were incubated or not with human IFN-γ (20 ng/ml) for 24 h. Data are expressed as mean ± SD. Comparisons between experimental groups were performed by one-way ANOVA test followed by the Tukey post hoc test