Exploring and Targeting the Tumor Immune Microenvironment of Neuroblastoma.

Pediatric neuroblastoma is a heterogenous disease that accounts for significant morbidity and mortality in children. Deep genomic and transcriptomic profiling of patient tumors has revealed a low mutational burden and a paucity of therapeutic targets. Furthermore, different molecular subtypes, such as amplification, have been associated with adverse outcomes. Using whole transcriptome sequencing, we previously explored the immune microenvironment of neuroblastoma subtypes and discovered its association with clinical outcome. Specifically, we found that patients with tumors infiltrated by higher levels of cytotoxic lymphocytes had a better overall survival. Additionally, we found that a high gene expression signature in -non-amplified tumors is an independent predictor of adverse outcome. However, signatures of tumor infiltrating cytotoxic immune cells in this subtype of tumors predict an improved outcome. While this is clinically informative, it does not provide a full picture of the dynamics underlying the biology of tumor immune microenvironment and how to use this information to improve patient outcomes. Here, we highlight our previous work and current approaches using immunotherapy in neuroblastoma and explore our current understanding of the immune biology of these tumors. We further describe how this correlates with patient outcome, and how this information can be used to develop novel immunotherapeutic strategies for pediatric patients with neuroblastoma.