SOS1i+MEKi combination treatment suppresses KPCY tumor growth in vivo and alters T cell infiltration in the TME. A, Experiment design of treatment schedule. B, Tumor volume (mm³) of individual tumors in mice for indicated tumor clone. TGI is indicated comparing vehicle with SOS1i+MEKi for each tumor clone at day 5. Unpaired Student t test performed with SD shown, n = 3–5 per group (*<0.05, **<0.01, ***<0.001). C, Representative IHC images of formalin-fixed paraffin-embedded section of each KPCY lines harvested at day 10 showing CD8⁺ staining. D, Scatter dot plots/graph showing density of IHC CD8⁺ in the KPCY TME (as in C) of individual mice harvested at day 5 and day 10 after treatment of vehicle (blue n = 2) and SOS1i+MEKi (red, n = 3). Student t test performed (**<0.01). E, Growth curves showing tumor volume of TC5 in vivo after start of treatment of vehicle, SOS1i, MEKi, or combination of SOS1i+MEKi. Arrows indicate days of treatment. TGI is indicated comparing vehicle with all other treatments. Multiple comparison ANOVA performed with SD shown, n = 5 per group (*<0.05). F, Bar graph showing composition of CD8⁺ T cells in CD45⁺ cells in TC5 clone after 8 days of treatment with vehicle, SOS1i, MEKi, or combination of SOS1i+MEKi (n = 5). Multiple comparison ANOVA performed (* = 0.05). G, Bar plot summarizing CD8⁺ T cell composition as �45⁺ in indicated tumor. L = left flank, R = right flank. Multiple comparison ANOVA performed with SD shown (ns = nonsignificant, ** = 0.01).
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Norgard et al. (2024) studied this question.
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