Abstract
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 MYCN 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 MYCN gene expression signature in MYCN-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.
Highlights
Neuroblastoma is derived from the developing sympathetic nervous system and is the most common extracranial solid tumor of childhood
In order to better characterize the phenotype of infiltrating T-cells, we examined co-expression of a panel of 7 exhaustion marker genes in combination with the cytotoxic immune cell signatures in a subset of MYCN-NA neuroblastoma tumors and observed a positive correlation between immune exhaustion and cytotoxic activity [12]
Cluster 1 tumors are from ultra-high-risk patients with MYCN-A tumors, which are characterized by a “cold” tumor microenvironment (TME) with few immune cell infiltrates (Table 1 and Figures 2C-F and 3)
Summary
Neuroblastoma is derived from the developing sympathetic nervous system and is the most common extracranial solid tumor of childhood. Our group has demonstrated that a subset of high-risk MYCN-not-amplified (MYCNNA) neuroblastomas have increased T-cell infiltration, suggesting the presence of antigenic targets and an active anti-tumor immune response [11,12]. This suggested that the presence of activated cytotoxic immune cells is prognostic in highrisk patients with MYCN-NA tumors expressing a high
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
