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

Ombretta Melaiu, Marco Chierici, Valeria Lucarini, Giuseppe Jurman, Libenzio Adrian Conti, Rita Vito, Renata Boldrini, Loredana Cifaldi, Aurora Castellano, Cesare Furlanello, Vincenzo Barnaba, Franco Locatelli and Doriana Fruci ()
Additional contact information
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
Vincenzo Barnaba: Cellular and Molecular Immunology Unit, Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari, Sapienza University of Rome
Franco Locatelli: Ospedale Pediatrico Bambino Gesù, IRCCS
Doriana Fruci: Ospedale Pediatrico Bambino Gesù, IRCCS

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19781-y

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