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IDO1(+) Paneth cells promote immune escape of colorectal cancer
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244549/ https://www.ncbi.nlm.nih.gov/pubmed/32444775 http://dx.doi.org/10.1038/s42003-020-0989-y |
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author | Pflügler, Sandra Svinka, Jasmin Scharf, Irene Crncec, Ilija Filipits, Martin Charoentong, Pornpimol Tschurtschenthaler, Markus Kenner, Lukas Awad, Monira Stift, Judith Schernthanner, Marina Bischl, Romana Herndler-Brandstetter, Dietmar Glitzner, Elisabeth Moll, Herwig P. Casanova, Emilio Timelthaler, Gerald Sibilia, Maria Gnant, Michael Lax, Sigurd Thaler, Josef Müller, Mathias Strobl, Birgit Mohr, Thomas Kaser, Arthur Trajanoski, Zlatko Heller, Gerwin Eferl, Robert |
author_facet | Pflügler, Sandra Svinka, Jasmin Scharf, Irene Crncec, Ilija Filipits, Martin Charoentong, Pornpimol Tschurtschenthaler, Markus Kenner, Lukas Awad, Monira Stift, Judith Schernthanner, Marina Bischl, Romana Herndler-Brandstetter, Dietmar Glitzner, Elisabeth Moll, Herwig P. Casanova, Emilio Timelthaler, Gerald Sibilia, Maria Gnant, Michael Lax, Sigurd Thaler, Josef Müller, Mathias Strobl, Birgit Mohr, Thomas Kaser, Arthur Trajanoski, Zlatko Heller, Gerwin Eferl, Robert |
author_sort | Pflügler, Sandra |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7244549 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72445492020-06-04 IDO1(+) Paneth cells promote immune escape of colorectal cancer Pflügler, Sandra Svinka, Jasmin Scharf, Irene Crncec, Ilija Filipits, Martin Charoentong, Pornpimol Tschurtschenthaler, Markus Kenner, Lukas Awad, Monira Stift, Judith Schernthanner, Marina Bischl, Romana Herndler-Brandstetter, Dietmar Glitzner, Elisabeth Moll, Herwig P. Casanova, Emilio Timelthaler, Gerald Sibilia, Maria Gnant, Michael Lax, Sigurd Thaler, Josef Müller, Mathias Strobl, Birgit Mohr, Thomas Kaser, Arthur Trajanoski, Zlatko Heller, Gerwin Eferl, Robert Commun Biol Article 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. Nature Publishing Group UK 2020-05-22 /pmc/articles/PMC7244549/ /pubmed/32444775 http://dx.doi.org/10.1038/s42003-020-0989-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Pflügler, Sandra Svinka, Jasmin Scharf, Irene Crncec, Ilija Filipits, Martin Charoentong, Pornpimol Tschurtschenthaler, Markus Kenner, Lukas Awad, Monira Stift, Judith Schernthanner, Marina Bischl, Romana Herndler-Brandstetter, Dietmar Glitzner, Elisabeth Moll, Herwig P. Casanova, Emilio Timelthaler, Gerald Sibilia, Maria Gnant, Michael Lax, Sigurd Thaler, Josef Müller, Mathias Strobl, Birgit Mohr, Thomas Kaser, Arthur Trajanoski, Zlatko Heller, Gerwin Eferl, Robert IDO1(+) Paneth cells promote immune escape of colorectal cancer |
title | IDO1(+) Paneth cells promote immune escape of colorectal cancer |
title_full | IDO1(+) Paneth cells promote immune escape of colorectal cancer |
title_fullStr | IDO1(+) Paneth cells promote immune escape of colorectal cancer |
title_full_unstemmed | IDO1(+) Paneth cells promote immune escape of colorectal cancer |
title_short | IDO1(+) Paneth cells promote immune escape of colorectal cancer |
title_sort | ido1(+) paneth cells promote immune escape of colorectal cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244549/ https://www.ncbi.nlm.nih.gov/pubmed/32444775 http://dx.doi.org/10.1038/s42003-020-0989-y |
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