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.

Raieli S., Di Renzo D., Lampis S., Amadesi C., Montemurro L., Pession A., et al. (2021). MYCN Drives a Tumor Immunosuppressive Environment Which Impacts Survival in Neuroblastoma. FRONTIERS IN ONCOLOGY, 11, 1-12 [10.3389/fonc.2021.625207].

MYCN Drives a Tumor Immunosuppressive Environment Which Impacts Survival in Neuroblastoma

Lampis S.
Formal Analysis
;
Montemurro L.
Methodology
;
Pession A.
Writing – Review & Editing
;
Hrelia P.
Writing – Review & Editing
;
Tonelli R.
Ultimo
Supervision
2021

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.
2021
Raieli S., Di Renzo D., Lampis S., Amadesi C., Montemurro L., Pession A., et al. (2021). MYCN Drives a Tumor Immunosuppressive Environment Which Impacts Survival in Neuroblastoma. FRONTIERS IN ONCOLOGY, 11, 1-12 [10.3389/fonc.2021.625207].
Raieli S.; Di Renzo D.; Lampis S.; Amadesi C.; Montemurro L.; Pession A.; Hrelia P.; Fischer M.; Tonelli R.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/840315
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