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

Author

Listed:
  • Nicoletta Caronni

    (International Centre for Genetic Engineering and Biotechnology, ICGEB
    IRCCS San Raffaele Scientific Institute)

  • 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
    Humanitas Clinical and Research Center-IRCCS)

  • Tiziana Schioppa

    (University of Brescia
    Humanitas Clinical and Research Center-IRCCS)

  • Emilia Maria Cristina Mazza

    (University of Modena and Reggio Emilia
    Humanitas Clinical and Research Center-IRCCS)

  • Licio Collavin

    (University of Trieste)

  • Serena Zacchigna

    (International Centre for Genetic Engineering and Biotechnology (ICGEB)
    University of Trieste)

  • Renato Ostuni

    (IRCCS San Raffaele Scientific Institute
    Vita-Salute San Raffaele University)

  • Pierre Guermonprez

    (King’s College London)

  • William Vermi

    (University of Brescia
    Washington University School of Medicine, St Louis)

  • Florent Ginhoux

    (Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)
    Shanghai JiaoTong University School of Medicine
    SingHealth Duke-NUS Academic Medical Centre)

  • Silvio Bicciato

    (University of Modena and Reggio Emilia)

  • Shigekatzu Nagata

    (Osaka University)

  • Federica Benvenuti

    (International Centre for Genetic Engineering and Biotechnology, ICGEB)

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.

Suggested Citation

  • Nicoletta Caronni & Giulia Maria Piperno & Francesca Simoncello & Oriana Romano & Simone Vodret & Yuichi Yanagihashi & Regine Dress & Charles-Antoine Dutertre & Mattia Bugatti & Pierre Bourdeley & Ann, 2021. "TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22535-z
    DOI: 10.1038/s41467-021-22535-z
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    Cited by:

    1. Lucía López & Luciano Gastón Morosi & Federica Terza & Pierre Bourdely & Giuseppe Rospo & Roberto Amadio & Giulia Maria Piperno & Valentina Russo & Camilla Volponi & Simone Vodret & Sonal Joshi & Fran, 2024. "Dendritic cell-targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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