SMAD4 and cancer: In colorectal cancer, loss of Smad4 facilitates liver metastasis by tumor accumulation of myeloid cells [37] and promotes cancer progression by increasing myeloid‐derived suppressor cells recruitment.[38] Different from colorectal cancer, our findings suggest that Smad4 loss enhanced PDAC tumor immunogenicity by eliciting DNA damage‐induced tumor‐intrinsic IFN‐I signaling and promoted immune cell infiltration.