Bibliographic Details
| Title: |
MYCN Drives a Tumor Immunosuppressive Environment Which Impacts Survival in Neuroblastoma |
| Authors: |
Salvatore Raieli, Daniele Di Renzo, Silvia Lampis, Camilla Amadesi, Luca Montemurro, Andrea Pession, Patrizia Hrelia, Matthias Fischer, Roberto Tonelli |
| Source: |
Frontiers in Oncology, Vol 11 (2021) |
| Publisher Information: |
Frontiers Media S.A., 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
MYCN, immune system, neuroblastoma, immune signature, immune network, anti-MYCN antigene PNA, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2234-943X |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fonc.2021.625207/full; https://doaj.org/toc/2234-943X |
| DOI: |
10.3389/fonc.2021.625207 |
| Access URL: |
https://doaj.org/article/bad6d4a7273842c689a925b87929773e |
| Accession Number: |
edsdoj.bad6d4a7273842c689a925b87929773e |
| Database: |
Directory of Open Access Journals |
