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IDO1 + Paneth cells promote immune escape of colorectal cancer

Published version
Peer-reviewed

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Authors

Pflügler, Sandra 
Svinka, Jasmin 
Scharf, Irene 
Crncec, Ilija 

Abstract

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.

Description

Keywords

Article, /631/67, /631/67/580, /631/67/1504/1885, /38/91, /45/41, /64/60, /96/95, article

Journal Title

Communications Biology

Conference Name

Journal ISSN

2399-3642

Volume Title

3

Publisher

Nature Publishing Group UK
Sponsorship
Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) (P29222-B28, W1212-P21, F4709-B20, SFB F6106)