Figure 7.

Combination therapy with MEK1/2 inhibitor and TLR7 agonist reduces melanoma progression in vivo. (A) Flow cytometry analysis of B16F10 apoptosis cultured alone or co-cultured with WT or Irf1^−/− BMDM. Cells were stimulated with R848 in the presence or absence of MEKi-U for 48 h. Data are means ± SD from 4 independent experiments. (B–D) WT or Irf1^−/− mice bearing subcutaneous (s.c.) B16F10 melanoma tumors were treated with MEKi-A or intratumoral (i.t.) R848 or both as indicated in (B). (C,D) Survival analysis (C) and tumor growth (D) of WT or Irf1^−/− melanoma-bearing mice treated with MEKi-A and/or R848. Data from at least 9 mice/group are pooled from 2 to 3 independent experiments. (E) Heat map showing mRNA expression of 36 genes identified with significant associations between their expression levels and patient survival. Data presented are from individuals with overall survival shorter than 321 days (n = 50) or longer than 4,407 days (n = 50). *P < 0.05, **P < 0.01, ***P < 0.001 by unpaired Welch's t-test (A), Cox regression analysis (C), or log-rank test (C,E).