| Literature DB >> 35120601 |
Aftab Alam1, Eric Levanduski1, Parker Denz1, Helena Solleiro Villavicencio1, Maulasri Bhatta1, Lamees Alhorebi1, Yali Zhang2, Eduardo Cortes Gomez2, Brian Morreale1, Sharon Senchanthisai1, Jun Li3, Steven G Turowski4, Sandra Sexton5, Sheila Jani Sait6, Prashant K Singh7, Jianmin Wang2, Anirban Maitra8, Pawel Kalinski9, Ronald A DePinho10, Huamin Wang11, Wenting Liao12, Scott I Abrams1, Brahm H Segal13, Prasenjit Dey14.
Abstract
TH2 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 KrasG12D increases IL-33 expression in pancreatic ductal adenocarcinoma (PDAC) cells, which recruits and activates TH2 and ILC2 cells. Correspondingly, cancer-cell-specific deletion of IL-33 reduces TH2 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 TH2 and ILC2 infiltration and increases survival. Consistently, high IL-33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identify therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL-33.Entities:
Keywords: IL-33; ILC2; Kras; PDAC; TH2; anti-fungal therapy; fungal mycobiome; innate lymphoid cells; intratumor-microbiome; type 2 immune response
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Year: 2022 PMID： 35120601 PMCID： PMC8847236 DOI： 10.1016/j.ccell.2022.01.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743