Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Raieli, Salvatore UNSPECIFIED UNSPECIFIED UNSPECIFIED Di Renzo, Daniele UNSPECIFIED UNSPECIFIED UNSPECIFIED Lampis, Silvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Amadesi, Camilla UNSPECIFIED UNSPECIFIED UNSPECIFIED Montemurro, Luca UNSPECIFIED UNSPECIFIED UNSPECIFIED Pession, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Hrelia, Patrizia UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Tonelli, Roberto UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language N-MYC; THERAPY; CELLS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58699