Lineage dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and -independent immunotherapeutic targets.

ABSTRACT:

Background

Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)-like cells and therapy-resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state-specific targetable cell surface proteins.

Methods

We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets. Targets were validated with ChIP-sequencing, immunoblotting, and flow cytometry in neuroblastoma cell lines and isogenic ADRN-to-MES transition cell line models. Finally, we evaluated the activity of MES-specific agents in vivo and in vi

SUBMITTER: Kendsersky NM 

PROVIDER: S-EPMC12187457 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature