Figure 5.
WEE1 inhibition improves the sensitivity of brachyury high/p21-low carcinoma cells. (A) Western blot analysis of brachyury expression in three clonally derived MC38 cell populations expressing low (Lo), intermediate (Int), or high (Hi) levels of the human brachyury transgene. (B) Sensitivity to lysis by p15E-specific cytotoxic CD8+ T cells, which have been left untreated (left panel) or were pre-treated with CMA to inhibit their ability to lyse targets in a perforin-dependent manner (right panel). (C) Sensitivity of MC38 clones to indicated doses of recombinant TNF-related apoptosis-inducing ligand (TRAIL). (D) Western blot analysis of brachyury expression in the MC38 pCMV and pBr isogenic cell pair. (E) Lysis of the MC38 tumor pair following WEE1 inhibition with indicated doses of MK-1775 by p15E-specific T cells (E:T ratio 50:1) expanded from either wild-type mice (left panel) or perforin-deficient animals (right panel), or (F) TRAIL (125 ng/mL). The data depicting the lysis of the MC38 pCMV and pBr cell lines are representative of two independent experiments.
