Raieli, Salvatore, Di Renzo, Daniele, Lampis, Silvia, Amadesi, Camilla, Montemurro, Luca, Pession, Andrea, Hrelia, Patrizia, Fischer, Matthias and Tonelli, Roberto (2021). MYCN Drives a Tumor Immunosuppressive Environment Which Impacts Survival in Neuroblastoma. Front. Oncol., 11. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2234-943X

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Abstract

A wide range of malignancies presents MYCN amplification (MNA) or dysregulation. MYCN is associated with poor prognosis and its over-expression leads to several dysregulations including metabolic reprogramming, mitochondria alteration, and cancer stem cell phenotype. Some hints suggest that MYCN overexpression leads to cancer immune-escape. However, this relationship presents various open questions. Our work investigated in details the relationship of MYCN with the immune system, finding a correlated immune-suppressive phenotype in neuroblastoma (NB) and different cancers where MYCN is up-regulated. We found a downregulated Th1-lymphocytes/M1-Macrophages axis and upregulated Th2-lymphocytes/M2-macrophages in MNA NB patients. Moreover, we unveiled a complex immune network orchestrated by N-Myc and we identified 16 genes modules associated to MNA NB. We also identified a MYCN-associated immune signature that has a prognostic value in NB and recapitulates clinical features. Our signature also discriminates patients with poor survival in non-MNA NB patients where MYCN expression is not discriminative. Finally, we showed that targeted inhibition of MYCN by BGA002 (anti-MYCN antigene PNA) is able to restore NK sensibility in MYCN-expressing NB cells. Overall, our study unveils a MYCN-driven immune network in NB and shows a therapeutic option to restore sensibility to immune cells.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Raieli, SalvatoreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Renzo, DanieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lampis, SilviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amadesi, CamillaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montemurro, LucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pession, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hrelia, PatriziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tonelli, RobertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-586994
DOI: 10.3389/fonc.2021.625207
Journal or Publication Title: Front. Oncol.
Volume: 11
Date: 2021
Publisher: FRONTIERS MEDIA SA
Place of Publication: LAUSANNE
ISSN: 2234-943X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
N-MYC; THERAPY; CELLSMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58699

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