Document Type
Article
Publication Date
11-23-2021
Publication Title
Cell Rep
Keywords
JGM
JAX Source
Cell Rep 2021 Nov 23; 37(8):110047
Volume
37
Issue
8
First Page
110047
Last Page
110047
ISSN
2211-1247
PMID
34818552
DOI
https://doi.org/10.1016/j.celrep.2021.110047
Abstract
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.
Recommended Citation
Brohl A,
Sindiri S,
Wei J,
Milewski D,
Chou H,
Song Y,
Wen X,
Kumar J,
Reardon H,
Mudunuri U,
Collins J,
Nagaraj S,
Gangalapudi V,
Tyagi M,
Zhu Y,
Masih K,
Yohe M,
Shern J,
Qi Y,
Guha U,
Catchpoole D,
Orentas R,
Kuznetsov I,
Llosa N,
Ligon J,
Turpin B,
Leino D,
Iwata S,
Andrulis I,
Wunder J,
Toledo S,
Meltzer P,
Lau C,
Teicher B,
Magnan H,
Ladanyi M,
Khan J.
Immuno-transcriptomic profiling of extracranial pediatric solid malignancies. Cell Rep 2021 Nov 23; 37(8):110047
Comments
This is an open access article under the CC BY license.