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The mycobiome-immune axis: The next frontier in pancreatic cancer

Xin Li1, Deepak Saxena2

  • 1Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Urology, NYU Grossman School of Medicine, New York, NY 10016, USA.

Cancer Cell
|February 15, 2022
PubMed

Insights

Researchers found that the cytokine IL-33 attracts immune cells to pancreatic tumors. Targeting this cytokine or the fungi triggering it slowed pancreatic cancer growth and improved survival.

Area of Science:

  • Oncology
  • Immunology
  • Microbiology

Background:

  • The tumor microenvironment plays a critical role in cancer progression.
  • The role of the fungal microbiome (mycobiome) in cancer is an emerging area of research.
  • Interleukin-33 (IL-33) is a cytokine involved in immune responses.

Purpose of the Study:

  • To investigate the role of the intratumoral mycobiome in pancreatic ductal adenocarcinoma (PDAC).
  • To identify specific molecular mechanisms linking the mycobiome to tumor progression.
  • To explore potential therapeutic targets for PDAC.

Main Methods:

  • Analysis of the intratumoral mycobiome in PDAC samples.
  • Investigating the release and function of IL-33 in response to fungal presence.
  • Utilizing genetic depletion of fungi and gene deletion of IL-33 in preclinical models of PDAC.
  • Assessing tumor progression and survival rates in response to interventions.

Main Results:

  • The intratumoral mycobiome was identified as a driver of inflammation in PDAC.
  • IL-33 was found to be released as a chemoattractant for type 2 immune cells in response to fungi.
  • Depletion of fungi significantly reduced tumor progression.
  • Deletion of IL-33 in cancer cells also decreased tumor progression and enhanced survival.

Conclusions:

  • The intratumoral mycobiome, via IL-33, promotes PDAC progression.
  • IL-33 acts as a crucial link between fungal presence and immune cell recruitment in PDAC.
  • Targeting the mycobiome or IL-33 presents a promising therapeutic strategy for pancreatic cancer.

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