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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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.
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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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