Two independent preclinical studies revealed complementary immune and metabolic mechanisms that may be leveraged in pancreatic ductal adenocarcinoma (PDAC). One team reported that targeted epigenetic therapy stabilizes GATA6‑dependent MHC class I expression, boosting antitumor T‑cell responses in PDAC models. The second study identified the inflammasome protein ASC as a regulator linking innate immune sensing to mitochondrial metabolism in pancreatic tumor cells. Both groups published mechanistic data showing how modulating epigenetic states or innate immune signaling reshapes tumor immunogenicity and metabolic vulnerabilities. The epigenetic approach aims to restore antigen presentation; the ASC work ties inflammasome components to mitochondrial function and tumor bioenergetics. These findings offer dual paths for combination strategies—epigenetic modulators or inflammasome‑targeted agents paired with immunotherapies—to potentially overcome PDAC’s immune‑cold microenvironment. Translational challenges include delivery, patient selection biomarkers, and safety in clinical testing.