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Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma

Author

Listed:
  • Ombretta Melaiu

    (Ospedale Pediatrico Bambino Gesù, IRCCS)

  • Marco Chierici

    (Fondazione Bruno Kessler)

  • Valeria Lucarini

    (Ospedale Pediatrico Bambino Gesù, IRCCS)

  • Giuseppe Jurman

    (Fondazione Bruno Kessler)

  • Libenzio Adrian Conti

    (Confocal microscopy, Core Facility, Research Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS)

  • Rita Vito

    (Bambino Gesù Children’s Hospital)

  • Renata Boldrini

    (Bambino Gesù Children’s Hospital)

  • Loredana Cifaldi

    (Ospedale Pediatrico Bambino Gesù, IRCCS)

  • Aurora Castellano

    (Ospedale Pediatrico Bambino Gesù, IRCCS)

  • Cesare Furlanello

    (Fondazione Bruno Kessler
    HK3 Lab)

  • Vincenzo Barnaba

    (Cellular and Molecular Immunology Unit, Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari, Sapienza University of Rome
    Istituto Pasteur Italia-Fondazione Cenci Bolognetti)

  • Franco Locatelli

    (Ospedale Pediatrico Bambino Gesù, IRCCS
    Sapienza University of Rome)

  • Doriana Fruci

    (Ospedale Pediatrico Bambino Gesù, IRCCS)

Abstract

Tumor-infiltrating lymphocytes play an essential role in improving clinical outcome of neuroblastoma (NB) patients, but their relationship with other tumor-infiltrating immune cells in the T cell-inflamed tumors remains poorly investigated. Here we show that dendritic cells (DCs) and natural killer (NK) cells are positively correlated with T-cell infiltration in human NB, both at transcriptional and protein levels, and associate with a favorable prognosis. Multiplex imaging displays DC/NK/T cell conjugates in the tumor microenvironment of low-risk NB. Remarkably, this connection is further strengthened by the identification of gene signatures related to DCs and NK cells able to predict survival of NB patients and strongly correlate with the expression of PD-1 and PD-L1. In summary, our findings unveil a key prognostic role of DCs and NK cells and indicate their related gene signatures as promising tools for the identification of clinical biomarkers to better define risk stratification and survival of NB patients.

Suggested Citation

  • Ombretta Melaiu & Marco Chierici & Valeria Lucarini & Giuseppe Jurman & Libenzio Adrian Conti & Rita Vito & Renata Boldrini & Loredana Cifaldi & Aurora Castellano & Cesare Furlanello & Vincenzo Barnab, 2020. "Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19781-y
    DOI: 10.1038/s41467-020-19781-y
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    Cited by:

    1. Irfete S. Fetahu & Wolfgang Esser-Skala & Rohit Dnyansagar & Samuel Sindelar & Fikret Rifatbegovic & Andrea Bileck & Lukas Skos & Eva Bozsaky & Daria Lazic & Lisa Shaw & Marcus Tötzl & Dora Tarlungean, 2023. "Single-cell transcriptomics and epigenomics unravel the role of monocytes in neuroblastoma bone marrow metastasis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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