Age-related alterations in immune contexture are associated with aggressiveness in Rhabdomyosarcoma

Patrizia Gasparini, Orazio Fortunato, Loris De Cecco, Michela Casanova, Maria Federica Iannó, Andrea Carenzo, Giovanni Centonze, Massimo Milione, Paola Collini, Mattia Boeri, Matteo Dugo, Chiara Gargiuli, Mavis Mensah, Miriam Segale, Luca Bergamaschi, Stefano Chiaravalli, Maria Luisa Sensi, Maura Massimino, Gabriella Sozzi, Andrea Ferrari

Research output: Contribution to journalArticlepeer-review

Abstract

Adolescents and young adults (AYA) with rhabdomyosarcoma (RMS) form a subgroup of patients whose optimal clinical management and access to care remain a challenge and whose survival lacks behind that of children diagnosed with histologically similar tumors. Understanding the tumor biology that differentiates children from AYA-RMS could provide critical information and drive new initiatives to improve the final outcome. MicroRNA (miRNA) and gene expression profiling (GEP) was evaluated in a RMS cohort of 49 tumor and 15 non-neoplastic tissues. miRNAs analysis identified miR-223 over-expression and miR-431 down-regulation in AYA, validated by Real-Time PCR and miRNA in situ hybridization (ISH). GEP analysis detected 793 age-correlated genes in tumors, of which 194 were anti-correlated. NOTCH2, FGFR1/2 were significantly down-modulated in AYA-RMS. miR-223 was associated with up-regulation of epithelial mesenchymal translation (EMT) and inflammatory pathways, whereas miR-431 was correlated to myogenic differentiation and muscle metabolism. GEP showed an increase in genes associated with CD4 memory resting cells and a decrease in genes associated with γδ T-cells in AYA-RMS. Immunohistochemistry (IHC) analysis demonstrated an increase of infiltrated CD4, CD8, and neutrophils in AYA-RMS tumors. Our results show that aggressiveness of AYA-RMS could be explained by differences in microenvironmental signal modulation mediated by tumor cells, suggesting a fundamental role of immune contexture in AYA-RMS development.

Original languageEnglish
Article number1380
JournalCancers
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 2019

Keywords

  • Adolescents
  • Gene expression
  • Immune contexture
  • MiRNA
  • Pediatric tumors
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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