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

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. Mitchell, Huang-ge Zhang, Yan Li, Robert C. G. Martin, Eric C. Rouchka and Jun Yan ()
Additional contact information
Anne E. Geller: University of Louisville
Rejeena Shrestha: University of Louisville
Matthew R. Woeste: University of Louisville
Haixun Guo: University of Louisville
Xiaoling Hu: University of Louisville
Chuanlin Ding: University of Louisville
Kalina Andreeva: University of Louisville
Julia H. Chariker: 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: University of Louisville
Eric C. Rouchka: University of Louisville
Jun Yan: University of Louisville

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28407-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28407-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28407-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().