Fig. 1
Braf mutant tumors relapse on vemurafenib with evidence of MAPK pathway re-activation and immune modulation. a Maximum percent tumor volume change in 75 animals treated with vemurafenib, twice a day via oral gavage at 50 mg/kg. Dotted line indicates ~30% regression. b Progression-free survival plot of vehicle and vemurafenib-treated animals. Animals were classified as progressed when their tumor size exceeded 30% of their initial biopsy value. c Schematic representation of tumor growth curve over time while on vemurafenib, showing initial biopsy (IB) and progressed biopsy (VPr) sample time points. d Sum of normalized 2−dCt values of MAPK target genes (Dusp4, Dusp6, Etv1, Etv4, Etv5, Fosl1, Phlda1, Spry2, and Spry4) plotted as percent of IB for V3d(n = 5), V12d(n = 6), and VPr(n = 75) samples. e FACS analysis of CD8 + PD1 + cells, plotted as a percent of total CD8 + cells for C(n = 3) and VPr(n = 3) samples. f Luminex analysis of IFNγ expression from C(n = 7), V12d(n = 5), and VPr(n = 7) tumors. g Progression-free survival plot of control vehicle (n = 14), vemurafenib (n = 33), and vemurafenib + α-PD-L1 (n = 9)-treated animals. Animals were classified as progressed when their tumor burden reached 30% above their initial biopsy value. Data are plotted as the mean ± SD for d–f. P-values in a by log-rank (Mantel–Cox) test. *p < 0.05, **p < 0.005 by t-test in e, f. C: control vehicle-treated samples; IB: initial biopsy; V3d: 3 day vemurafenib-treated samples; V12d: 12-day vemurafenib-treated samples; VPr: vemurafenib-progressed samples
