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Single-Cell Profiling of the Microenvironment in High-Risk Neuroblastoma.

Yuxuan Xu1, Jinsheng Ding1, Zhenyu Shi1

  • 1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Tianjin, China.

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Summary

Targeting the tumor microenvironment (TME) in high-risk neuroblastoma (HR-NB) offers new hope. This study identifies specific immunosuppressive cells and novel therapeutic targets within the HR-NB TME, paving the way for improved immunotherapies.

Keywords:
high‐risk neuroblastomaimmunotherapyprognostic signaturesingle‐cell RNA sequencingtumor microenvironment

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Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • High-risk neuroblastoma (HR-NB) patient outcomes remain poor despite treatment advances.
  • The tumor microenvironment (TME) is increasingly recognized as a critical factor in HR-NB progression and treatment resistance.
  • Understanding the cellular and molecular composition of the HR-NB TME is essential for developing effective therapies.

Purpose of the Study:

  • To investigate the cellular landscape of the TME in HR-NB using single-cell RNA sequencing.
  • To identify specific TME cell populations and molecular targets associated with HR-NB progression and immune suppression.
  • To develop a prognostic signature for HR-NB based on immune-related genes.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) of 16 NB samples from HR-NB and intermediate-/low-risk NB patients.
  • Bioinformatic analysis including SCENIC to identify regulatory networks.
  • Construction and validation of an immune-related gene-based prognostic model.

Main Results:

  • Proliferating CD8+ T cells, H2AFZ+ macrophages, and proliferating B cells were enriched in HR-NB and exhibited immunosuppressive roles.
  • LAG3 and HAVCR2 were identified as potential immunotherapeutic targets.
  • An immune-related risk model based on five genes (BIRC5, UBE2C, CDKN3, TK1, PTTG1) demonstrated clinical prediction value.

Conclusions:

  • Single-cell analysis revealed key TME components driving immune suppression and progression in HR-NB.
  • Identified novel immunotherapeutic targets (LAG3, HAVCR2) and a prognostic signature for HR-NB.
  • Findings provide a foundation for developing novel immunotherapies for HR-NB.