TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses
Acquisition of cell-associated tumor antigens by type 1 dendritic cells (cDC1) is essential to induce and sustain tumor specific CD8(+) T cells via cross-presentation. Here we show that capture and engulfment of cell associated antigens by tissue resident lung cDC1 is inhibited during progression of...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046802/ https://www.ncbi.nlm.nih.gov/pubmed/33854047 http://dx.doi.org/10.1038/s41467-021-22535-z |
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author | Caronni, Nicoletta Piperno, Giulia Maria Simoncello, Francesca Romano, Oriana Vodret, Simone Yanagihashi, Yuichi Dress, Regine Dutertre, Charles-Antoine Bugatti, Mattia Bourdeley, Pierre Del Prete, Annalisa Schioppa, Tiziana Mazza, Emilia Maria Cristina Collavin, Licio Zacchigna, Serena Ostuni, Renato Guermonprez, Pierre Vermi, William Ginhoux, Florent Bicciato, Silvio Nagata, Shigekatzu Benvenuti, Federica |
author_facet | Caronni, Nicoletta Piperno, Giulia Maria Simoncello, Francesca Romano, Oriana Vodret, Simone Yanagihashi, Yuichi Dress, Regine Dutertre, Charles-Antoine Bugatti, Mattia Bourdeley, Pierre Del Prete, Annalisa Schioppa, Tiziana Mazza, Emilia Maria Cristina Collavin, Licio Zacchigna, Serena Ostuni, Renato Guermonprez, Pierre Vermi, William Ginhoux, Florent Bicciato, Silvio Nagata, Shigekatzu Benvenuti, Federica |
author_sort | Caronni, Nicoletta |
collection | PubMed |
description | Acquisition of cell-associated tumor antigens by type 1 dendritic cells (cDC1) is essential to induce and sustain tumor specific CD8(+) T cells via cross-presentation. Here we show that capture and engulfment of cell associated antigens by tissue resident lung cDC1 is inhibited during progression of mouse lung tumors. Mechanistically, loss of phagocytosis is linked to tumor-mediated downregulation of the phosphatidylserine receptor TIM4, that is highly expressed in normal lung resident cDC1. TIM4 receptor blockade and conditional cDC1 deletion impair activation of tumor specific CD8(+) T cells and promote tumor progression. In human lung adenocarcinomas, TIM4 transcripts increase the prognostic value of a cDC1 signature and predict responses to PD-1 treatment. Thus, TIM4 on lung resident cDC1 contributes to immune surveillance and its expression is suppressed in advanced tumors. |
format | Online Article Text |
id | pubmed-8046802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80468022021-04-30 TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses Caronni, Nicoletta Piperno, Giulia Maria Simoncello, Francesca Romano, Oriana Vodret, Simone Yanagihashi, Yuichi Dress, Regine Dutertre, Charles-Antoine Bugatti, Mattia Bourdeley, Pierre Del Prete, Annalisa Schioppa, Tiziana Mazza, Emilia Maria Cristina Collavin, Licio Zacchigna, Serena Ostuni, Renato Guermonprez, Pierre Vermi, William Ginhoux, Florent Bicciato, Silvio Nagata, Shigekatzu Benvenuti, Federica Nat Commun Article Acquisition of cell-associated tumor antigens by type 1 dendritic cells (cDC1) is essential to induce and sustain tumor specific CD8(+) T cells via cross-presentation. Here we show that capture and engulfment of cell associated antigens by tissue resident lung cDC1 is inhibited during progression of mouse lung tumors. Mechanistically, loss of phagocytosis is linked to tumor-mediated downregulation of the phosphatidylserine receptor TIM4, that is highly expressed in normal lung resident cDC1. TIM4 receptor blockade and conditional cDC1 deletion impair activation of tumor specific CD8(+) T cells and promote tumor progression. In human lung adenocarcinomas, TIM4 transcripts increase the prognostic value of a cDC1 signature and predict responses to PD-1 treatment. Thus, TIM4 on lung resident cDC1 contributes to immune surveillance and its expression is suppressed in advanced tumors. Nature Publishing Group UK 2021-04-14 /pmc/articles/PMC8046802/ /pubmed/33854047 http://dx.doi.org/10.1038/s41467-021-22535-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Caronni, Nicoletta Piperno, Giulia Maria Simoncello, Francesca Romano, Oriana Vodret, Simone Yanagihashi, Yuichi Dress, Regine Dutertre, Charles-Antoine Bugatti, Mattia Bourdeley, Pierre Del Prete, Annalisa Schioppa, Tiziana Mazza, Emilia Maria Cristina Collavin, Licio Zacchigna, Serena Ostuni, Renato Guermonprez, Pierre Vermi, William Ginhoux, Florent Bicciato, Silvio Nagata, Shigekatzu Benvenuti, Federica TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses |
title | TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses |
title_full | TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses |
title_fullStr | TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses |
title_full_unstemmed | TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses |
title_short | TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses |
title_sort | tim4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046802/ https://www.ncbi.nlm.nih.gov/pubmed/33854047 http://dx.doi.org/10.1038/s41467-021-22535-z |
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