SignificanceWhile CD8+T cells are essential for antitumor immunity, tumors often evade CD8+T cell surveillance by immunosuppression. Recent study has shown that tumor-induced β-catenin activation in DCs suppresses CD8+T cell immunity by inhibiting cross-priming, suggesting that activation of β-catenin in DCs might be a key mechanism tumors use to achieve immunosuppression. This report identified mTOR/IL-10 signaling as a previously unidentified mechanism for β-catenin–dependent inhibition of cross-priming. Surprisingly, our study also revealed that β-catenin in DCs was required for CD8+T cell maintenance post-clonal expansion, suggesting that β-catenin exerts opposite functions during different stages of CD8+T cell responses. Based on these findings, we have demonstrated selectively manipulating β-catenin signaling as a feasible strategy to improve DC vaccine efficacy.