Immunotherapy Options for Neuroblastoma: What is on the Horizon?

Neuroblastoma is the most commonly seen extracranial tumor in children originating from the sympathetic nervous system. It is responsible for approximately 20% of cancer-related deaths in the pediatric population, making this malignancy one of the worst scenarios. Patients are classified into low or high-risk groups based on their tumor's age at diagnosis, histological tumor stage, and genetic status. Despite the good outcomes of current therapy modalities in low-risk neuroblastoma patients, investigation of novel treatment paradigms for high-risk neuroblastoma patients is necessary.

Current therapy for high-risk neuroblastoma patients consists of chemotherapy, surgical resection, radiotherapy, the combination of high-dose chemotherapy with autologous hematopoietic stem-cell transplantation, isotretinoin, immunotherapy with anti-GD2 monoclonal antibodies and cytokines, and radioimmunotherapy. These options achieve high rates of overall survival, yet the challenges of improving anti-GD2 immunotherapy remain. Low mutational burden, restricted T-cell infiltration, and downregulated MHC-1 expression are critical factors that pose significant challenges to the success of immunotherapy. It is crucial to address these hurdles to ensure the effectiveness of the treatment.

There has been a significant research focus on overcoming the immunologic impediments that hinder progress in treatment and describing novel target molecules for neuroblastoma. This paper provides a comprehensive review of the immunological landscape of the malignancy under study and highlights the latest potent approaches.