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Factors Influencing Immunotherapy Response in Neuroblastoma: From Tumor Microenvironment to Combination Strategies.

Created on 12 Sep 2026

Authors

Xiaoran Du, Rui Dong, Kuiran Dong

Published in

Cells. Volume 15. Issue 5. Feb 28, 2026. Epub Feb 28, 2026.

Abstract

Neuroblastoma is the most common extracranial solid tumor in children, and the prognosis for high-risk patients remains dismal. Immunotherapies, represented by anti-GD2 monoclonal antibodies and chimeric antigen receptor T cells (CAR-T), have significantly improved the survival of high-risk neuroblastoma patients and become part of standard therapy. However, their efficacy exhibits significant inter-individual heterogeneity, with some patients showing primary resistance or secondary relapse. This review aims to analyze the multi-faceted factors influencing the response to immunotherapy in neuroblastoma, including: (1) the inherent immunosuppressive properties of the tumor microenvironment, such as infiltration of myeloid-derived suppressor cells and tumor-associated macrophages, as well as checkpoint molecules and metabolic barriers; (2) tumor cell-intrinsic characteristics, such as low tumor mutational burden, MYCN amplification-associated downregulation of MHC-I, and heterogeneity of GD2 antigen expression; (3) host factors, such as systemic immune status and Fc receptor polymorphisms; and (4) treatment-related factors, such as combination strategies and the development of novel immunotherapeutic products. A deep understanding of these interrelated factors is crucial for developing predictive biomarkers, designing novel combination strategies and next-generation immunotherapies, and ultimately achieving precise immunotherapy for neuroblastoma.

PMID:
41827873
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.

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