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.

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

Title
IDO1+ Paneth cells promote immune escape of colorectal cancer
Author
Pflügler Sandra 1 ; Svinka Jasmin 1 ; Scharf, Irene 1 ; Crncec Ilija 1 ; Filipits Martin 1   VIAFID ORCID Logo  ; Charoentong Pornpimol 2 ; Tschurtschenthaler, Markus 3   VIAFID ORCID Logo  ; Kenner Lukas 4 ; Awad Monira 1 ; Stift, Judith 5 ; Schernthanner Marina 1 ; Bischl Romana 1 ; Herndler-Brandstetter Dietmar 1 ; Glitzner Elisabeth 1 ; Moll, Herwig P 6   VIAFID ORCID Logo  ; Casanova Emilio 7   VIAFID ORCID Logo  ; Timelthaler Gerald 1 ; Sibilia, Maria 1 ; Gnant, Michael 8   VIAFID ORCID Logo  ; Lax Sigurd 9 ; Thaler, Josef 10 ; Müller Mathias 11   VIAFID ORCID Logo  ; Strobl Birgit 11   VIAFID ORCID Logo  ; Mohr, Thomas 1   VIAFID ORCID Logo  ; Kaser, Arthur 12 ; Trajanoski Zlatko 13   VIAFID ORCID Logo  ; Heller Gerwin 14 ; Eferl, Robert 1   VIAFID ORCID Logo 

1  Medical University of Vienna and Comprehensive Cancer Center, Institute of Cancer Research, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492) 
2  Medical University Innsbruck, Biocenter, Institute of Bioinformatics, Innsbruck, Austria (GRID:grid.5361.1) (ISNI:0000 0000 8853 2677); University Hospital Heidelberg, Department of Medical Oncology, National Center for Tumor diseases, Heidelberg, Germany (GRID:grid.5253.1) (ISNI:0000 0001 0328 4908); German Cancer Research Center (DKFZ), Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
3  University of Cambridge, Division of Gastroenterology and Hepatology, Department of Medicine, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Technical University of Munich, Center for Translational Cancer Research (TranslaTUM), Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966) 
4  Ludwig Boltzmann Institute for Cancer Research LBICR, Vienna, Austria (GRID:grid.454387.9) (ISNI:0000 0004 0436 8814); Medical University of Vienna, Institute of Clinical Pathology, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492); University of Veterinary Medicine Vienna, Department of Laboratory Animal Pathology, Vienna, Austria (GRID:grid.6583.8) (ISNI:0000 0000 9686 6466) 
5  Medical University of Vienna, Institute of Clinical Pathology, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492) 
6  Medical University of Vienna, Department of Physiology, Center of Physiology and Pharmacology, Comprehensive Cancer Center (CCC), Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492) 
7  Ludwig Boltzmann Institute for Cancer Research LBICR, Vienna, Austria (GRID:grid.454387.9) (ISNI:0000 0004 0436 8814); Medical University of Vienna, Department of Physiology, Center of Physiology and Pharmacology, Comprehensive Cancer Center (CCC), Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492) 
8  Medical University of Vienna, Department of Surgery, Breast Health Center, Comprehensive Cancer Center, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492) 
9  Hospital Graz II, Department of Pathology, Graz, Austria (GRID:grid.22937.3d); Johannes Kepler University, Institute of Pathology and Molecular Pathology, Linz, Austria (GRID:grid.9970.7) (ISNI:0000 0001 1941 5140) 
10  Klinikum Wels-Grieskirchen, Department of Internal Medicine IV, Wels, Austria (GRID:grid.459707.8) (ISNI:0000 0004 0522 7001) 
11  University of Veterinary Medicine Vienna, Institute of Animal Breeding and Genetics, Vienna, Austria (GRID:grid.6583.8) (ISNI:0000 0000 9686 6466) 
12  University of Cambridge, Division of Gastroenterology and Hepatology, Department of Medicine, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
13  Medical University Innsbruck, Biocenter, Institute of Bioinformatics, Innsbruck, Austria (GRID:grid.5361.1) (ISNI:0000 0000 8853 2677) 
14  Medical University of Vienna and Comprehensive Cancer Center, Division of Oncology, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-020-0989-y
ProQuest document ID
2405840506
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.