Two studies unveiled complementary mechanisms that could reshape pancreatic ductal adenocarcinoma strategies. One team (Nature Communications) identified the inflammasome protein ASC as a regulator linking innate immune sensing to mitochondrial metabolism in pancreatic cancer cells. ASC altered bioenergetics and supported tumor growth. A separate study demonstrated that targeted epigenetic modulation can stabilize GATA6‑dependent MHCI expression in PDAC, restoring antigen presentation and enhancing antitumor immunity. Authors showed improved immune infiltration and checkpoint‑therapy synergy in preclinical models. Together, the findings suggest dual approaches—targeting metabolic‑immune nodes and reversing epigenetic suppression of MHCI—as potential combination strategies. Drug developers focusing on immunometabolism, epigenetic modifiers, and combination immunotherapies will evaluate these mechanisms for candidate prioritization and trial design.