Fig. 8

Agonist immunotherapy rescues T-cell effector functions in the presence of MEK inhibition. Mice bearing established AT3ova tumors were treated with vehicle, trametinib plus isotype control antibody and either α-4-1BB or α-OX-40 antibody alone; IP injection on day 0, or combination of trametinib and agonists. Changes in TIL populations (CD8⁺, CD4⁺ FOXP3⁻, CD4⁺ FOXP3⁺ T cells, macrophage, and MDSCs) were determined ex vivo by FACS analysis 4 days post treatment. a TIL frequency as a proportion of CD45⁺ live cells, b IFNγ cytokine production by T cells, c proliferation of T cells measured by Ki67 expression, and d frequency of macrophage (CD11b⁺, F4/80⁺) and MDSC (CD11b⁺, Ly6c⁺) subsets. Values were normalized to vehicle controls in each experiment. Data are expressed as fold change ± SEM for the number of positive cells and represents n = 5–10 mice per group, pooled from two independent experiments. P-values represent one-way ANOVA, post hoc Fisher’s LSD tests.*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001