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Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma

Author

Listed:
  • Rocky M. Barilla

    (New York University School of Medicine)

  • Brian Diskin

    (New York University School of Medicine)

  • Raul Caso Caso

    (New York University School of Medicine)

  • Ki Buom Lee

    (New York University School of Medicine)

  • Navyatha Mohan

    (New York University School of Medicine)

  • Chandan Buttar

    (New York University School of Medicine)

  • Salma Adam

    (New York University School of Medicine)

  • Zennur Sekendiz

    (New York University School of Medicine)

  • Junjie Wang

    (New York University School of Medicine)

  • Ruben D. Salas

    (New York University School of Medicine)

  • Marcelo F. Cassini

    (New York University School of Medicine)

  • Jason Karlen

    (New York University School of Medicine)

  • Belen Sundberg

    (New York University School of Medicine)

  • Hashem Akbar

    (New York University School of Medicine)

  • Dmitry Levchenko

    (New York University School of Medicine)

  • Inderdeep Gakhal

    (New York University School of Medicine)

  • Johana Gutierrez

    (New York University School of Medicine)

  • Wei Wang

    (New York University School of Medicine)

  • Mautin Hundeyin

    (New York University School of Medicine)

  • Alejandro Torres-Hernandez

    (New York University School of Medicine)

  • Joshua Leinwand

    (New York University School of Medicine)

  • Emma Kurz

    (New York University School of Medicine)

  • Juan A. Kochen Rossi

    (New York University School of Medicine)

  • Ankita Mishra

    (New York University School of Medicine)

  • Miguel Liria

    (New York University School of Medicine)

  • Gustavo Sanchez

    (New York University School of Medicine)

  • Jyoti Panta

    (New York University School of Medicine)

  • P’ng Loke

    (New York University School of Medicine)

  • Berk Aykut

    (New York University School of Medicine)

  • George Miller

    (New York University School of Medicine
    New York University School of Medicine)

Abstract

The drivers and the specification of CD4+ T cell differentiation in the tumor microenvironment and their contributions to tumor immunity or tolerance are incompletely understood. Using models of pancreatic ductal adenocarcinoma (PDA), we show that a distinct subset of tumor-infiltrating dendritic cells (DC) promotes PDA growth by directing a unique TH-program. Specifically, CD11b+CD103− DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3neg tumor-promoting IL-10+IL-17+IFNγ+ regulatory CD4+ T cells. The balance between this distinctive TH program and canonical FoxP3+ TREGS is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This TH-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b+CD103− DC promote CD4+ T cell tolerance in PDA which may underscore its resistance to immunotherapy.

Suggested Citation

  • Rocky M. Barilla & Brian Diskin & Raul Caso Caso & Ki Buom Lee & Navyatha Mohan & Chandan Buttar & Salma Adam & Zennur Sekendiz & Junjie Wang & Ruben D. Salas & Marcelo F. Cassini & Jason Karlen & Bel, 2019. "Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09416-2
    DOI: 10.1038/s41467-019-09416-2
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