Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer.

ABSTRACT: T_H2 cells and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as interleukin-4 (IL-4), IL-5, and IL-13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment are unknown. Here, we show that oncogenic Kras^G12D increases IL-33 expression in pancreatic ductal adenocarcinoma (PDAC) cells, which recruits and activates T_H2 and ILC2 cells. Correspondingly, cancer-cell-specific deletion of IL-33 reduces T_H2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, IL-33 secretion is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL-33 or anti-fungal treatment decreases T_H2 and ILC2 infiltration and increases survival. Consist

SUBMITTER: Alam A 

PROVIDER: S-EPMC8847236 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature