This study investigates how pancreatic ductal adenocarcinoma (PDAC) cells respond to and exploit different microenvironments within the pancreas, revealing that local tissue injury plays a key role in shaping tumor behavior and subtype identity. Using spatial transcriptomic mapping, multiplex protein profiling, and integrative analysis of human PDAC tissue combined with mouse models, the researchers identified distinct injury-associated lobular microniches, which are regions of acinar injury and inflammation that provide an environment for tumor cell invasion. Within these injured lobules, PDAC cells predominantly exhibited the classical subtype, characterized by epithelial differentiation and lower invasiveness. In contrast, tumor cells located in the fibrotic, desmoplastic stroma displayed a basal-like phenotype, which is more aggressive and resistant to treatment. Experimental models confirmed that when tumor cells infiltrate injured acinar regions, they can revert from basal-like to classical phenotype, indicating that the microenvironment actively drives phenotypic plasticity instead of promoting static tumor states. The study also found that these microniches have distinctive stromal and immune cells with inflammatory and repair-related signals, showing that PDAC diversity comes from interactions with specific tissue environments, not just genetic differences.