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 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.

Citation

Nicoletta Caronni, Giulia Maria Piperno, Francesca Simoncello, Oriana Romano, Simone Vodret, Yuichi Yanagihashi, Regine Dress, Charles-Antoine Dutertre, Mattia Bugatti, Pierre Bourdeley, Annalisa Del Prete, Tiziana Schioppa, Emilia Maria Cristina Mazza, Licio Collavin, Serena Zacchigna, Renato Ostuni, Pierre Guermonprez, William Vermi, Florent Ginhoux, Silvio Bicciato, Shigekatzu Nagata, Federica Benvenuti. TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses. Nature communications. 2021 Apr 14;12(1):2237

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PMID: 33854047

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