1. IDO1+ Paneth cells promote immune escape of colorectal cancer
- Author
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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], and Apollo-University Of Cambridge Repository
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631/67 ,631/67/1504/1885 ,Male ,0301 basic medicine ,Paneth Cells ,Colorectal cancer ,45/41 ,medicine.medical_treatment ,Medicine (miscellaneous) ,digestive system ,Article ,General Biochemistry, Genetics and Molecular Biology ,38/91 ,96/95 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Stroma ,Intestinal Neoplasms ,Immune Tolerance ,medicine ,Animals ,Indoleamine-Pyrrole 2,3,-Dioxygenase ,STAT1 ,lcsh:QH301-705.5 ,Cancer ,Mice, Knockout ,biology ,Immune escape ,Immunosuppression ,Immunotherapy ,medicine.disease ,digestive system diseases ,3. Good health ,Mice, Inbred C57BL ,Immunosurveillance ,STAT1 Transcription Factor ,030104 developmental biology ,lcsh:Biology (General) ,631/67/580 ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Tumour immunology ,64/60 ,Colorectal Neoplasms ,General Agricultural and Biological Sciences - 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.
- Published
- 2020
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