Fig. 9
MEK inhibition and agonist combination therapy in RAG and T-cell depletion models demonstrates the functional role of T cells in enhancing therapeutic responses. a, b RAG−/− mice (n = 8 per group) bearing established AT3ova tumors were treated with vehicle or trametinib via daily oral gavage for 20 days (AT3ova) and either 2A3 isotype control, α-4-1BB, or α-OX-40 antibody alone; four doses (AT3ova) via IP injection on days 0, 4, 8, and 12 or combination of trametinib and agonists. c WT C57BL/6 mice (n = 6 per group) bearing established AT3ova tumors were concurrently depleted of CD4 and CD8 T cells using depletion antibodies (200 µg/dose) on day −1, 0, 7, and 14 of treatment. d Matched non-depleted control groups of WT C57BL/6 mice (n = 6 per group) bearing established AT3ova tumors were also administered the same treatment schedule as described above for single and combination therapies. a–d Tumor growth volume (mm3) was monitored. Controls groups are duplicated between panels as these experiments were performed concurrently. Vehicle and trametinib arms are duplicated in a and b. P-values represent two-way ANOVA, post hoc Tuckey’s tests for tumor growth. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001
