Druggable epigenetic suppression of interferon-induced chemokine expression linked to MYCN amplification in neuroblastoma.

ABSTRACT:

Background

Amplification of the MYCN oncogene is a molecular hallmark of aggressive neuroblastoma (NB), a childhood cancer of the sympathetic nervous system. There is evidence that MYCN promotes a non-inflamed and T-cell infiltration-poor ('cold') tumor microenvironment (TME) by suppressing interferon signaling. This may explain, at least in part, why patients with NB seem to have little benefit from single-agent immune checkpoint blockade (ICB) therapy. Targeting MYCN or its effectors could be a strategy to convert a cold TME into a 'hot' (inflamed) TME and improve the efficacy of ICB therapy.

Methods

NB transcriptome analyses were used to identify epigenetic drivers of a T-cell infiltration-poor TME. Biological and molecular responses of NB cells to epigeneti

SUBMITTER: Seier JA 

PROVIDER: S-EPMC8141444 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature