Figure 1:

TME composition is associated with tumor subtype and patient clinical outcomes. A. Consensus clustering of 150 TARGET neuroblastoma samples based on their gene expression profiles identified 4 distinct clusters. B. Kaplan–Meier curves demonstrated significant difference in overall survival (OS) in all patients for the 4 clusters identified by consensus clustering in A. C. The MYCN-functional gene signature predicted the outcome of 92 TARGET high-risk patients with MYCN-NA neuroblastomas. Median MYCN-sig score was used to stratify the MYCN-NA patients into two groups used in the Kaplan–Meier plot. A significantly worse OS was observed for patients with a high MYCN-signature (MYCN-sig high) than for those with low MYCN-signature (MYCN-sig low). D. Single sample GSEA (ssGSEA) showed MYCN-NA tumors had higher immune scores, activated NK cell, CD8 T-cell, and cytolytic activity than those of MYCN-A or 4S tumors. Enrichment scores were z-scored, sorted, and plotted for each group of tumors. The red lines are median values for each plot. E. Kaplan-Meier survival analysis of high-risk TARGET patients with MYCN-NA tumors expressing a high MYCN-signature stratified by the scores of the activated NK cell or cytolytic signatures. The survival curves were obtained using a K-M optimization procedure, and samples with expression levels of activated NK cell or cytolytic signatures less than or equal to the optimal threshold were labeled as “NK_act low” or “Cytolytic low”. Samples with the expression level of the signatures greater than the threshold were labeled as “NK_act high” or “Cytolytic high”.