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MYCN Drives a Tumor Immunosuppressive Environment Which Impacts Survival in Neuroblastoma

Salvatore Raieli1, Daniele Di Renzo2, Silvia Lampis1

  • 1R&D Department, BIOGENERA SpA, Bologna, Italy.

Frontiers in Oncology
|March 15, 2021
PubMed

Insights

MYCN amplification drives an immune-suppressive phenotype in neuroblastoma (NB), characterized by altered immune cell balance. Targeting MYCN with BGA002 can restore immune cell sensitivity in NB.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • MYCN amplification (MNA) or dysregulation is prevalent in many cancers, correlating with poor prognosis.
  • MYCN overexpression is linked to metabolic reprogramming, mitochondrial alterations, cancer stem cell phenotypes, and potential immune evasion.

Purpose of the Study:

  • To investigate the intricate relationship between MYCN and the immune system, particularly in neuroblastoma (NB).
  • To identify MYCN-associated immune signatures and assess their prognostic value.
  • To evaluate the therapeutic potential of MYCN inhibition in restoring immune cell sensitivity.

Main Methods:

  • Analysis of immune cell populations (Th1/M1 vs. Th2/M2) in MNA NB patients.
  • Identification of gene modules associated with MNA NB.
  • Development and validation of a MYCN-associated immune signature.
  • Assessment of BGA002 (anti-MYCN PNA) efficacy in restoring NK cell sensitivity.

Main Results:

  • A correlated immune-suppressive phenotype was observed in NB and other MYCN-upregulated cancers.
  • Downregulation of Th1-lymphocytes/M1-Macrophages and upregulation of Th2-lymphocytes/M2-macrophages were found in MNA NB patients.
  • A novel MYCN-associated immune signature demonstrated prognostic value in NB and identified poor-prognosis patients.
  • Targeted MYCN inhibition by BGA002 restored NK cell sensitivity in MYCN-expressing NB cells.

Conclusions:

  • MYCN orchestrates a complex immune network leading to an immune-suppressive phenotype in NB.
  • The identified MYCN-associated immune signature is a valuable prognostic biomarker.
  • MYCN inhibition presents a therapeutic strategy to enhance anti-tumor immunity in NB.
Keywords:
MYCNMYCN blockinganti-MYCN antigene PNAimmune networkimmune signatureimmune systemneuroblastoma

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