Fig. 5

Selumetinib reverses anti-CTLA-4-mediated increases in Cox-2 and Arg1 expression within tumors. Following 8 days of treatment, the relative tumor expression levels of 92 genes were determined by qRT-PCR. a Volcano plots showing gene expression levels comparing selumetinib or anti-CTLA-4 treated samples versus control, or combination versus anti-CTLA-4 monotherapy. Down-regulated (green) and up-regulated (red) genes are highlighted. P-value boundary of 0.05 and fold-change boundaries of │1.5│ are shown as horizontal and vertical lines, respectively. Bar charts showing tumor expression levels of (b) Arg1 and (c) Cox-2 transcripts, following 1 or 8 days of treatment. Error bars represent 95% confidence intervals. d IHC analysis of two planes of tumor (100 μm apart) showing percent positive Arg1. Whiskers shown represents minima and maxima. One-tail Mann-Whitney test performed. * p < 0.05 (e) Representative Arg1 staining patterns in tumors using IHC. Studies contained 6 mice per treatment group