Abstract
The immune features in pediatric tumor are poorly explored. To characterize immune features of pediatric cancer, we performed an immunogenomic analysis of public database (TARGET) for pediatric solid tumor (PST) (n = 423) and pediatric hematological tumor (PHT) (n = 2302). We clustered PST and PHT samples into 5 subtypes (S1-S5) and 4 subtypes (H1-H4), respectively, based on immune features. In the PST cohort, cluster S1 with elevated expression of Wound_CSR (fibroblast core serum response in wound healing) and B cell signatures exhibited the worst overall survival. Conversely, cluster S4 (HR = 0.378, 95% CI: 0.24–0.59, P-value < 0.001) with down-regulated expression of these features was associated with prolonged survival. We also validated the prognostic significance of the S4 immune subtype in an independent neuroblastoma cohort from the ZJUCH (n = 127), which demonstrated favorable patient outcomes. In the PHT cohort, we observed that the relationships between immune clusters and prognosis differed between FLT3-ITD mutation-positive AML (AML-1) and FLT3-ITD mutation-negative AML (AML-2). In AML-1, cluster H2 featured upregulated infiltration of neutrophils, monocytes and antigen processing signatures, possibly leading to the worst overall survival. While in AML-2, cluster H2 exhibited a favorable outcome. The study highlights the potential of immune features as biomarkers for prognosis and treatment planning in pediatric cancers and provides novel insights into their immunological landscape.
Data availability
High-throughput sequencing and clinical data were acquired from the TARGET database through Genomic Data Commons (GDC) data portal (https://gdc.cancer.gov/). The neuroblastoma validation cohort (referred to as ZJUCH cohort) was obtained from Children’s Hospital Zhejiang University School of Medicine. The RNA-seq data of the ZJUCH cohort were available from the Genome Sequence Archive in National Genomics Data Center, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences under accession numbers HRA006359 and HRA007828.
Abbreviations
- PST:
-
Pediatric solid tumor
- PHT:
-
Pediatric hematological tumor
- NB:
-
Neuroblastoma
- AML:
-
Acute myeloid leukemia
- TIME:
-
Tumor immune microenvironment
- ALL:
-
Acute lymphoblastic leukemia
- OS:
-
Osteosarcoma
- WT:
-
Wilms tumor
- RT:
-
Rhabdoid tumor
- CCSK:
-
Clear cell sarcoma of kidney
- dbGaP:
-
Database of Genotypes and Phenotypes
- NIH:
-
National Institutes of Health
- TPM:
-
Transcripts per kilobase of exon per million mapped reads
- FPKM:
-
Fragments per kilobase of exon per million mapped fragments
- ssGSEA:
-
Single-sample gene set enrichment analysis
- GSEs:
-
Gene set enrichment scores
- QuSAGE:
-
Quantitative set analysis for gene expression
- GO:
-
Gene Ontology
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- DAWT:
-
Diffuse anaplastic Wilms tumor
- FHWT:
-
Favorable histology Wilms tumor
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Funding
This work was supported by grants (No. 82373971 and No. 32270853) from National Natural Science Foundation of China, a grant (No. 2023YFC2706100) from National Key R&D Program of China, grants (No. 2025C01106 and 2024C03181) from “Pioneer” and “Leading Goose” R&D Program of Zhejiang Province, grants (No. 2022KY1047 and No. 2024KY1428) from Medical Science and Technology Project of Zhejiang Province, a startup fund from Children’s Hospital, Zhejiang University School of Medicine, and a research fund from Cancer Center, Zhejiang University.
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T.T., S.N. and J.W. provided resources and obtained funding. T.T., S.N. and Q.H. conceived and supervised the study. T.T., Z.X. and J.Q. generated the data. T.T., Z.X., Q.H. and J.L. performed analysis. T.T. and Z.X. interpreted the data and wrote the main manuscript text. Z.X. prepared figures and tables. All authors reviewed and approved the final manuscript.
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Xia, Z., Hua, Q., Qian, J. et al. Immunogenomic classification reveals prognostic immune signatures in pediatric solid and hematological tumors. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44997-1
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DOI: https://doi.org/10.1038/s41598-026-44997-1
