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The induction of peripheral trained immunity in the pancreas incites anti-tumor activity to control pancreatic cancer progression

Author

Listed:
  • Anne E. Geller

    (University of Louisville
    University of Louisville)

  • Rejeena Shrestha

    (University of Louisville
    University of Louisville)

  • Matthew R. Woeste

    (University of Louisville
    University of Louisville
    University of Louisville)

  • Haixun Guo

    (University of Louisville)

  • Xiaoling Hu

    (University of Louisville)

  • Chuanlin Ding

    (University of Louisville)

  • Kalina Andreeva

    (University of Louisville
    University of Louisville)

  • Julia H. Chariker

    (University of Louisville
    University of Louisville)

  • Mingqian Zhou

    (University of Louisville)

  • David Tieri

    (University of Louisville)

  • Corey T. Watson

    (University of Louisville)

  • Robert A. Mitchell

    (University of Louisville)

  • Huang-ge Zhang

    (University of Louisville)

  • Yan Li

    (University of Louisville)

  • Robert C. G. Martin II

    (University of Louisville)

  • Eric C. Rouchka

    (University of Louisville
    University of Louisville)

  • Jun Yan

    (University of Louisville
    University of Louisville)

Abstract

Despite the remarkable success of immunotherapy in many types of cancer, pancreatic ductal adenocarcinoma has yet to benefit. Innate immune cells are critical to anti-tumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Here we demonstrate that yeast-derived particulate β-glucan, an inducer of trained immunity, traffics to the pancreas, which causes a CCR2-dependent influx of monocytes/macrophages to the pancreas that display features of trained immunity. These cells can be activated upon exposure to tumor cells and tumor-derived factors, and show enhanced cytotoxicity against pancreatic tumor cells. In orthotopic models of pancreatic ductal adenocarcinoma, β-glucan treated mice show significantly reduced tumor burden and prolonged survival, which is further enhanced when combined with immunotherapy. These findings characterize the dynamic mechanisms and localization of peripheral trained immunity and identify an application of trained immunity to cancer.

Suggested Citation

  • Anne E. Geller & Rejeena Shrestha & Matthew R. Woeste & Haixun Guo & Xiaoling Hu & Chuanlin Ding & Kalina Andreeva & Julia H. Chariker & Mingqian Zhou & David Tieri & Corey T. Watson & Robert A. Mitch, 2022. "The induction of peripheral trained immunity in the pancreas incites anti-tumor activity to control pancreatic cancer progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28407-4
    DOI: 10.1038/s41467-022-28407-4
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    References listed on IDEAS

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    1. Helen S. Goodridge & Christopher N. Reyes & Courtney A. Becker & Tamiko R. Katsumoto & Jun Ma & Andrea J. Wolf & Nandita Bose & Anissa S. H. Chan & Andrew S. Magee & Michael E. Danielson & Arthur Weis, 2011. "Activation of the innate immune receptor Dectin-1 upon formation of a ‘phagocytic synapse’," Nature, Nature, vol. 472(7344), pages 471-475, April.
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    1. Xiaowei Bian & Minna Piipponen & Zhuang Liu & Lihua Luo & Jennifer Geara & Yongjian Chen & Traimate Sangsuwan & Monica Maselli & Candice Diaz & Connor A. Bain & Evelien Eenjes & Maria Genander & Micha, 2024. "Epigenetic memory of radiotherapy in dermal fibroblasts impairs wound repair capacity in cancer survivors," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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