TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses

Nicoletta Caronni (), Giulia Maria Piperno, Francesca Simoncello, Oriana Romano, Simone Vodret, Yuichi Yanagihashi, Regine Dress, Charles-Antoine Dutertre, Mattia Bugatti, Pierre Bourdeley, Annalisa Prete, Tiziana Schioppa, Emilia Maria Cristina Mazza, Licio Collavin, Serena Zacchigna, Renato Ostuni, Pierre Guermonprez, William Vermi, Florent Ginhoux, Silvio Bicciato, Shigekatzu Nagata and Federica Benvenuti ()
Additional contact information
Nicoletta Caronni: International Centre for Genetic Engineering and Biotechnology, ICGEB
Giulia Maria Piperno: International Centre for Genetic Engineering and Biotechnology, ICGEB
Francesca Simoncello: International Centre for Genetic Engineering and Biotechnology, ICGEB
Oriana Romano: University of Modena and Reggio Emilia
Simone Vodret: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Yuichi Yanagihashi: Osaka University
Regine Dress: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)
Charles-Antoine Dutertre: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)
Mattia Bugatti: University of Brescia
Pierre Bourdeley: King’s College London
Annalisa Prete: University of Brescia
Tiziana Schioppa: University of Brescia
Emilia Maria Cristina Mazza: University of Modena and Reggio Emilia
Licio Collavin: University of Trieste
Serena Zacchigna: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Renato Ostuni: IRCCS San Raffaele Scientific Institute
Pierre Guermonprez: King’s College London
William Vermi: University of Brescia
Florent Ginhoux: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)
Silvio Bicciato: University of Modena and Reggio Emilia
Shigekatzu Nagata: Osaka University
Federica Benvenuti: International Centre for Genetic Engineering and Biotechnology, ICGEB

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-22535-z

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