Next Article in Journal
BRAF Mutations Classes I, II, and III in NSCLC Patients Included in the SLLIP Trial: The Need for a New Pre-Clinical Treatment Rationale
Previous Article in Journal
Observations on Solitary Versus Multiple Isolated Pancreatic Metastases of Renal Cell Carcinoma: Another Indication of a Seed and Soil Mechanism?
Open AccessFeature PaperArticle

Age-Related Alterations in Immune Contexture Are Associated with Aggressiveness in Rhabdomyosarcoma

1
Tumor Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
2
Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
3
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
4
Department of Diagnostic Pathology and from the Laboratory of Medicine of our Institute, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
*
Authors to whom correspondence should be addressed.
Patrizia Gasparini and Orazio Fortunato contributed equally to this work.
Andrea Ferrari and Gabriella Sozzi are co-last authors.
Cancers 2019, 11(9), 1380; https://doi.org/10.3390/cancers11091380
Received: 12 August 2019 / Revised: 6 September 2019 / Accepted: 11 September 2019 / Published: 17 September 2019
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. View Full-Text
Keywords: rhabdomyosarcoma; pediatric tumors; adolescents; miRNA; gene expression; immune contexture rhabdomyosarcoma; pediatric tumors; adolescents; miRNA; gene expression; immune contexture
Show Figures

Figure 1

MDPI and ACS Style

Gasparini, P.; Fortunato, O.; De Cecco, L.; Casanova, M.; Iannó, M.F.; Carenzo, A.; Centonze, G.; Milione, M.; Collini, P.; Boeri, M.; Dugo, M.; Gargiuli, C.; Mensah, M.; Segale, M.; Bergamaschi, L.; Chiaravalli, S.; Sensi, M.L.; Massimino, M.; Sozzi, G.; Ferrari, A. Age-Related Alterations in Immune Contexture Are Associated with Aggressiveness in Rhabdomyosarcoma. Cancers 2019, 11, 1380.

AMA Style

Gasparini P, Fortunato O, De Cecco L, Casanova M, Iannó MF, Carenzo A, Centonze G, Milione M, Collini P, Boeri M, Dugo M, Gargiuli C, Mensah M, Segale M, Bergamaschi L, Chiaravalli S, Sensi ML, Massimino M, Sozzi G, Ferrari A. Age-Related Alterations in Immune Contexture Are Associated with Aggressiveness in Rhabdomyosarcoma. Cancers. 2019; 11(9):1380.

Chicago/Turabian Style

Gasparini, Patrizia; Fortunato, Orazio; De Cecco, Loris; Casanova, Michela; Iannó, Maria F.; Carenzo, Andrea; Centonze, Giovanni; Milione, Massimo; Collini, Paola; Boeri, Mattia; Dugo, Matteo; Gargiuli, Chiara; Mensah, Mavis; Segale, Miriam; Bergamaschi, Luca; Chiaravalli, Stefano; Sensi, Maria L.; Massimino, Maura; Sozzi, Gabriella; Ferrari, Andrea. 2019. "Age-Related Alterations in Immune Contexture Are Associated with Aggressiveness in Rhabdomyosarcoma" Cancers 11, no. 9: 1380.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop