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

Nat Commun. 2020 Nov 25;11(1):5992. doi: 10.1038/s41467-020-19781-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • B7-H1 Antigen / metabolism
  • Child
  • Child, Preschool
  • Cohort Studies
  • Datasets as Topic
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Male
  • Middle Aged
  • Neuroblastoma / genetics
  • Neuroblastoma / immunology
  • Neuroblastoma / mortality*
  • Neuroblastoma / pathology
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism
  • RNA-Seq
  • Sensitivity and Specificity
  • Survival Rate
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transcriptome / immunology*
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor