The immune landscape of solid pediatric tumors

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.