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. Acquisition of dying tumor cell-associated antigens is an essential step for the initiation of anti-tumor immune response by conventional type 1 dendritic cells (cDC1). Here the authors show that the loss of TIM4 expression in lung tumor associated cDC1 is associated with less efficient uptake of cell associated antigens and reduction of CD8+T cell activation in advanced lung tumors.

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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 12:1(2021). [10.1038/s41467-021-22535-z]

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

Ostuni, Renato;
2021-01-01

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. Acquisition of dying tumor cell-associated antigens is an essential step for the initiation of anti-tumor immune response by conventional type 1 dendritic cells (cDC1). Here the authors show that the loss of TIM4 expression in lung tumor associated cDC1 is associated with less efficient uptake of cell associated antigens and reduction of CD8+T cell activation in advanced lung tumors.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/158580
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