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IDO1 + Paneth cells promote immune escape of colorectal cancer

Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying...

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Main Authors: Pflügler, Sandra (Author) , Svinka, Jasmin (Author) , Scharf, Irene (Author) , Crncec, Ilija (Author) , Filipits, Martin (Author) , Charoentong, Pornpimol (Author) , Tschurtschenthaler, Markus (Author) , Kenner, Lukas (Author) , Awad, Monira (Author) , Stift, Judith (Author) , Schernthanner, Marina (Author) , Bischl, Romana (Author) , Herndler-Brandstetter, Dietmar (Author) , Glitzner, Elisabeth (Author) , Moll, Herwig P. (Author) , Casanova, Emilio (Author) , Timelthaler, Gerald (Author) , Sibilia, Maria (Author) , Gnant, Michael (Author) , Lax, Sigurd (Author) , Thaler, Josef (Author) , Müller, Mathias (Author) , Strobl, Birgit (Author) , Mohr, Thomas (Author) , Kaser, Arthur (Author) , Trajanoski, Zlatko (Author) , Heller, Gerwin (Author) , Eferl, Robert (Author)
Format: Article (Journal)
Language:English
Published: 22 May 2020
In: Communications biology
Year: 2020, Volume: 3, Pages: 1-14
ISSN:2399-3642
DOI:10.1038/s42003-020-0989-y
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s42003-020-0989-y
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s42003-020-0989-y
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Author Notes:Sandra Pflügler, Jasmin Svinka, Irene Scharf, Ilija Crncec, Martin Filipits, Pornpimol Charoentong, Markus Tschurtschenthaler, Lukas Kenner, Monira Awad, Judith Stift, Marina Schernthanner, Romana Bischl, Dietmar Herndler-Brandstetter, Elisabeth Glitzner, Herwig P. Moll, Emilio Casanova, Gerald Timelthaler, Maria Sibilia, Michael Gnant, Sigurd Lax, Josef Thaler, Mathias Müller, Birgit Strobl, Thomas Mohr, Arthur Kaser, Zlatko Trajanoski, Gerwin Heller & Robert Eferl

MARC

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520 |a Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying mechanisms of immune escape are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1)+ Paneth cells in the stem cell niche of intestinal crypts and tumors, which promoted immune escape of colorectal cancer (CRC). Ido1 expression in Paneth cells was strictly Stat1 dependent. Loss of IDO1+ Paneth cells in murine intestinal adenomas with tumor cell-specific Stat1 deletion had profound effects on the intratumoral immune cell composition. Patient samples and TCGA expression data suggested corresponding cells in human colorectal tumors. Thus, our data uncovered an immune escape mechanism of CRC and identify IDO1+ Paneth cells as a target for immunotherapy. 
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