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Recent studies overwhelmingly show that microbiome is pervasive to tumor and play key role in immunotherapy response and reprograming tumor immune microenvironment (TIME). However, it remains unknown how microbiome facilitates the host-immune cell crosstalk and promote tumorigenesis. Our recent study in pancreatic ductal adenocarcinoma (PDAC) show that intratumor fungal microbiome facilitate the release of a damage associated molecular pattern (DAMP) molecule IL-33 from cancer cells. The secreted IL33 from cancer cells in turns recruits ILC2 and T_H2 cells which promotes PDAC tumorigenesis. However, the mechanism of fungal mediated IL-33 release from PDAC cells remains unknown. Our follow up studies using high throughput integrated proteomic profiling and immunoprecipitation revealed a group of exocyst complex proteins interacting with IL-33 in the presence of fungus. The exocyst …