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

Aftab Alam, Eric Levanduski, Parker Denz, Helena Solleiro Villavicencio, Maulasri Bhatta, Lamees Alhorebi, Yali Zhang, Eduardo Cortes Gomez, Brian Morreale, Sharon Senchanthisai, Jun Li, Steven G. Turowski, Sandra Sexton, Sheila Jani Sait, Prashant K. Singh, Jianmin Wang, Anirban Maitra, Pawel Kalinski, Ronald A. DePinho, Huamin WangWenting Liao, Scott I. Abrams, Brahm H. Segal, Prasenjit Dey

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)153-167.e11
JournalCancer cell
Issue number2
StatePublished - Feb 14 2022
Externally publishedYes


  • IL-33
  • ILC2
  • Kras
  • PDAC
  • TH2
  • anti-fungal therapy
  • fungal mycobiome
  • innate lymphoid cells
  • intratumor-microbiome
  • type 2 immune response

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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