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IDO1+ Paneth cells promote immune escape of colorectal cancer

Authors :
Josef Thaler
Irene Scharf
Monira Awad
Elisabeth Glitzner
Maria Sibilia
Gerwin Heller
Marina Schernthanner
Birgit Strobl
Emilio Casanova
Arthur Kaser
Mathias Müller
Thomas Mohr
Jasmin Svinka
Ilija Crncec
Gerald Timelthaler
Romana Bischl
Zlatko Trajanoski
Robert Eferl
Herwig P. Moll
Sigurd Lax
Lukas Kenner
Sandra Pflügler
Michael Gnant
Martin Filipits
Dietmar Herndler-Brandstetter
Pornpimol Charoentong
Judith Stift
Markus Tschurtschenthaler
Filipits, Martin [0000-0003-2847-4534]
Tschurtschenthaler, Markus [0000-0002-0060-4790]
Moll, Herwig P [0000-0001-6438-9068]
Casanova, Emilio [0000-0001-7992-5361]
Gnant, Michael [0000-0003-1002-2118]
Müller, Mathias [0000-0002-7879-3552]
Strobl, Birgit [0000-0001-5716-3212]
Mohr, Thomas [0000-0002-1933-847X]
Trajanoski, Zlatko [0000-0002-0636-7351]
Eferl, Robert [0000-0002-6074-7144]
Apollo - University of Cambridge Repository
Moll, Herwig P. [0000-0001-6438-9068]
Apollo-University Of Cambridge Repository
Source :
Communications Biology, Communications Biology, Vol 3, Iss 1, Pp 1-14 (2020)
Publication Year :
2020
Publisher :
Springer Science and Business Media LLC, 2020.

Abstract

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.<br />Pflügler, Svinka et al. identify a subset of Paneth cells in mouse intestinal crypts and tumors, which express the immune checkpoint molecule Ido1 in a Stat1-dependent manner and promote tumor growth. Gene expression data from human colorectal cancer (CRC) suggest that a similar population is present in human cancer and opens the door for further studies of immune escape mechanisms in CRC.

Details

ISSN :
23993642
Volume :
3
Database :
OpenAIRE
Journal :
Communications Biology
Accession number :
edsair.doi.dedup.....c77346f1d4b8bd985c9f2d0438fa7c0a
Full Text :
https://doi.org/10.1038/s42003-020-0989-y