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Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

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Brohl, Andrew S 
Sindiri, Sivasish 
Wei, Jun S 
Milewski, David 
Chou, Hsien-Chao 


We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches.



PRAME, RNA sequencing, T cell receptor, adoptive cell therapy, immunogenomics, immunopeptidomics, pediatric oncology, tumor-infiltrating lymphocytes, Adolescent, Antigens, Neoplasm, Cell Line, Tumor, Child, Child, Preschool, Female, Gene Expression, Gene Expression Profiling, Humans, Immune Checkpoint Proteins, Immunogenetics, Immunotherapy, Adoptive, Infant, Lymphocytes, Tumor-Infiltrating, Male, Neoplasms, Receptors, Antigen, T-Cell, Transcriptome, Tumor Microenvironment, Exome Sequencing

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Elsevier BV
Intramural NIH HHS (ZIA BC010806, ZIA BC010593, ZIA BC011002, Z01 SC010366, Z99 CA999999, ZIA SC010366, Z01 BC010593, Z01 BC011002, ZIA BC010998)