The role of immunotherapy in the treatment of neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in children. The prognosis for high-risk disease remains poor despite multimodal therapy, including chemotherapy, surgical resection, radiotherapy, and autologous stem-cell transplantation. Immunotherapy has improved outcomes remarkably, particularly using anti-GD2 monoclonal antibodies, which are now established as standard maintenance therapy. Combination regimens of cytokines and isotretinoin have enhanced survival, and chemo-immunotherapy has demonstrated superior response rates in relapsed/refractory settings. The aim of treatment with next-generation antibodies, such as humanized or Fc-engineered formats, is to reduce toxicity and improve efficacy. GD2-based vaccines and cellular therapies, including CAR-T cells, NK/NKT cell therapy, and bispecific antibody-armed T cells, have shown promising activity, particularly for minimal residual disease. However, challenges such as GD2 downregulation, an immunosuppressive tumor microenvironment, and manufacturing constraints persist. Future strategies may involve multimodal immunotherapy integrating antibodies, vaccines, and cellular platforms with precise patient selection and microenvironment modulation. Immunotherapy is reshaping neuroblastoma treatment, with the potential to achieve both deeper remission and long-term disease control.