IDO1+ Paneth cells promote immune escape of colorectal cancer

Autor: 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
Přispěvatelé: 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
Rok vydání: 2020
Předmět:
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
Zdroj: Communications Biology
Communications Biology, Vol 3, Iss 1, Pp 1-14 (2020)
ISSN: 2399-3642
DOI: 10.1038/s42003-020-0989-y
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: