The immune landscape of solid pediatric tumors
Related Experiment Video
Updated: Sep 20, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Shimaa Sherif1,2, Jessica Roelands2,3, William Mifsud4,5
1College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
Insights
Pediatric tumors show immune profiles similar to adult cancers. Classifying tumors by immune disposition can improve diagnostics and identify potential immunotherapies.
Area of Science:
- Pediatric oncology
- Cancer immunology
- Tumor microenvironment
Background:
- The prognostic role of tumor microenvironment (TME) orientation is established in adult cancers but understudied in pediatric tumors.
- Understanding TME in pediatric cancers is crucial for improving patient outcomes.
Purpose of the Study:
- To systematically analyze the immune microenvironment of common pediatric solid tumors.
- To explore similarities and differences in immune disposition between pediatric and adult tumors.
- To identify immune subtypes with distinct prognostic implications in pediatric cancers.
Main Methods:
- Systematic analysis of RNA sequencing data from the TARGET initiative for 408 pediatric patients across five tumor types (Wilms tumor, neuroblastoma, osteosarcoma, clear cell sarcoma of the kidney, rhabdoid tumor of the kidney).
- Assessment of the Immunologic Constant of Rejection (ICR) score to capture Th1/cytotoxic responses.
- Gene set enrichment analysis (ssGSEA) and clustering of immune traits to define immune subtypes and compare survival outcomes.
Main Results:
- A higher ICR score correlated with better survival in osteosarcoma and high-risk neuroblastoma (without MYCN amplification), but poorer survival in Wilms tumor.
- Clustering of immune traits identified six pediatric immune subtypes (S1-S6), mirroring five principal modules found in adult tumors (TCGA), with distinct survival outcomes.
- The S2 subtype exhibited the best overall survival (low wound healing, high Th1, low Th2), while S4 showed the opposite. WNT/Beta-catenin pathway upregulation in osteosarcoma was linked to worse outcomes and reduced T-cell infiltration.
Conclusions:
- Extracranial pediatric tumors can be classified based on their immune disposition, showing parallels with adult tumors.
- Immunological parameters offer potential for refining diagnostic and prognostic biomarkers in pediatric oncology.
- Immune profiling may help identify pediatric tumors responsive to immunotherapy.
Background:
Large immunogenomic analyses have demonstrated the prognostic role of the functional orientation of the tumor microenvironment in adult solid tumors, this variable has been poorly explored in the pediatric counterpart.
Methods:
We performed a systematic analysis of public RNAseq data (TARGET) for five pediatric tumor types (408 patients): Wilms tumor (WLM), neuroblastoma (NBL), osteosarcoma (OS), clear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RT). We assessed the performance of the Immunologic Constant of Rejection (ICR), which captures an active Th1/cytotoxic response. We also performed gene set enrichment analysis (ssGSEA) and clustered more than 100 well characterized immune traits to define immune subtypes and compared their outcome.
Results:
A higher ICR score was associated with better survival in OS and high risk NBL without MYCN amplification but with poorer survival in WLM. Clustering of immune traits revealed the same five principal modules previously described in adult tumors (TCGA). These modules divided pediatric patients into six immune subtypes (S1-S6) with distinct survival outcomes. The S2 cluster showed the best overall survival, characterized by low enrichment of the wound healing signature, high Th1, and low Th2 infiltration, while the reverse was observed in S4. Upregulation of the WNT/Beta-catenin pathway was associated with unfavorable outcomes and decreased T-cell infiltration in OS.
Conclusions:
We demonstrated that extracranial pediatric tumors could be classified according to their immune disposition, unveiling similarities with adults' tumors. Immunological parameters might be explored to refine diagnostic and prognostic biomarkers and to identify potential immune-responsive tumors.
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