Neuroblastoma (NB) is one of the most common causes of pediatric cancer mortality. Cancer is well known for its complexity and wide variety of presentations. At its worst, NB presents with early metastasis and resistance to therapies. It contains complex molecular and genetic features and has an immunosuppressive microenvironment that forms a complex case that is fatal in around 50% of affected patients, even with the current multimodal treatment standard for high-risk neuroblastoma (HR-NB). This has highlighted a need for comprehensive molecular understanding of the tumor, as well as multi-targeted therapeutic approaches. Current targets that remain a focus for NB include GD2 Disialoganglioside (GD2), v-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN), glypican 2 (GPC2), B7 Homolog 3 (B7-H3) also known as CD276, and Anaplastic Lymphoma Kinase (ALK). Recent advances covered in this review include further developments in anti-GD2 immunotherapy, targeted therapy for ALK-driven tumors, Chimeric Antigen Receptor T-cell therapy (CAR-T), combination therapies, and other immunotherapies. This review aims to compile the most up-to-date information on the recent advances in the molecular landscape of immunotherapy in a comprehensive manner to understand and identify the shortcomings and future directions for treatment targets of HR-NB.

Immunotherapy, Neuroblastoma, Molecular pathogenesis, Precision oncology