FIGURE 5 from Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with Combined SOS1 and MEK Inhibition for Improved Immunotherapy Response

Combination of SOS1i+MEKi inhibitors sensitize cold KPCY tumors to confer prolonged TGI and immune memory. A, Schematic of treatment regimen of SOS1i+MEKi with aPD-1, aCTLA-4, and aCD40. B, Tumor volume from day postimplantation. T cell low clone (TC4) were implanted subcutaneously into C57Bl/6 mice (n = 10–11 mice per group) and treated when tumors reached 40–100 mm³. C, Waterfall plots from mice bearing tumors comparing start of therapy (day 12) with 48 hours after final dose (day 23; n = 10–11 mice per group). D, Table summarizing results of outcomes after treatment of TGI at day 23, tumor regressions at day 23, complete responders at day 23, tumor regressions at end of experiment day 60, and complete responders at end of experiment day 60. Columns are in order of B. E, Kaplan–Meier survival curves from mice implanted with TC4 clone and treated with indicated therapy. Median survival in days shown in parenthesis. n = 10–11 mice per group (* = 0.05, ** = 0.01, *** = 0.001). F, Survival of mice cured by SOS1i+MEKi+aPD-1+aCTLA-4+aCD40 therapy in B were rechallenged with a secondary tumor on the opposing flank. Kaplan–Meier survival curves of cured mice (n = 3) or age-matched controls (n = 5).