IL33: Shaping the Pancreatic Tumor Microenvironment

This research uncovers a critical role for the cytokine interleukin-33 (IL33) in pancreatic cancer progression, driven by oncogenic KRAS-dependent signaling in cancer-associated fibroblasts (CAFs). IL33 expression, initiated and sustained by epithelial KRAS mutations, orchestrates profound changes in the tumor microenvironment, including fibroblast activation and modulation of immune cells. Using IL33 knockout models, researchers demonstrated that eliminating stromal IL33 reprograms the microenvironment, leading to increased infiltration and activation of CD8+ T cells and significantly reduced tumor growth. These findings highlight stromal IL33 as a key player in pancreatic cancer's immunosuppressive environment and present it as a promising therapeutic target to enhance anti-tumor immunity.