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Predictive Immune Modeling of Solid Tumors
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Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

Andrew S Brohl1, Sivasish Sindiri2, Jun S Wei2

  • 1Sarcoma Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

Cell Reports
|November 24, 2021
PubMed
Summary
This summary is machine-generated.

This study analyzed pediatric solid tumors to map immune cell infiltration and T-cell receptor diversity. Findings reveal immune profiles predict survival in osteosarcoma and identify new targets for pediatric cancer immunotherapy.

Keywords:
PRAMERNA sequencingT cell receptoradoptive cell therapyimmunogenomicsimmunopeptidomicspediatric oncologytumor-infiltrating lymphocytes

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Area of Science:

  • Immunogenomics
  • Pediatric Oncology
  • Cancer Immunology

Background:

  • Pediatric extracranial solid tumors are diverse, with varying immune microenvironments.
  • Understanding immune cell infiltration and T-cell receptor (TCR) dynamics is crucial for developing effective immunotherapies.

Purpose of the Study:

  • To conduct an immunogenomics analysis of pediatric extracranial solid tumors.
  • To characterize immune cell patterns, TCR clonal expansion, and immune checkpoints.
  • To identify novel immunotherapeutic targets for pediatric cancers.

Main Methods:

  • Whole-transcriptome sequencing of 657 pediatric cancer samples and 131 cell lines.
  • Comparative analysis with 147 normal tissue samples.
  • Orthogonal immunopeptidomics approach for target validation.

Main Results:

  • Significant variation in tumor-infiltrating lymphocytes and TCR counts across and within pediatric cancer types.
  • TCR counts are predictive of survival in osteosarcoma.
  • Identification of potential immunotherapeutic targets, including PRAME, across multiple pediatric cancers.

Conclusions:

  • Immune profiles offer prognostic value in pediatric cancers like osteosarcoma.
  • Parallel immuno-transcriptomic and immunopeptidomic approaches provide a framework for targeting extracranial solid tumors.
  • PRAME is validated as a multi-pediatric cancer immunotherapeutic target.