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Immuno-transcriptomic profiling of extracranial pediatric solid malignancies

  1. Author:
    Brohl, Andrew S
    Sindiri, Sivasish
    Wei, Jun S
    Milewski, David
    Chou, Hsien-Chao
    Song, Young K
    Wen, Xinyu
    Kumar, Jeetendra
    Reardon, Hue V
    Mudunuri,Uma
    Collins,Jack
    Nagaraj, Sushma
    Gangalapudi, Vineela
    Tyagi, Manoj
    Zhu, Yuelin J
    Masih, Katherine E
    Yohe, Marielle E
    Shern, Jack F
    Qi, Yue
    Guha, Udayan
    Catchpoole, Daniel
    Orentas, Rimas J
    Kuznetsov, Igor B
    Llosa, Nicolas J
    Ligon, John A
    Turpin, Brian K
    Leino, Daniel G
    Iwata, Shintaro
    Andrulis, Irene L
    Wunder, Jay S
    Toledo, Silvia R C
    Meltzer, Paul S
    Lau, Ching
    Teicher, Beverly A
    Magnan, Heather
    Ladanyi, Marc
    Khan, Javed

  2. Author Address

    Sarcoma Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA., Genetics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA., Advanced Biomedical Computational Science, Leidos Biomedical Research Inc., NCI Campus at Frederick, Frederick, MD 21702, USA., Laboratory of Pathology, CCR, NCI, NIH, Bethesda, MD 20892, USA., Genetics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Pediatric Oncology Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA., Thoracic and GI Malignancies Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA., The Tumour Bank, Children 39;s Cancer Research Unit, Kids Research Institute, The Children 39;s Hospital at Westmead, Westmead, NSW, Australia., Ben Towne Center for Childhood Cancer Research, Seattle Children 39;s Research Institute, Seattle, WA 98101, USA; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98101, USA., Cancer Research Center and Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY 12144, USA., Pediatric Oncology, John Hopkins University School of Medicine, Baltimore, MD 21218, USA., Division of Oncology, Cincinnati Children 39;s Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA., Chiba Cancer Center, Chiba, Japan., Lunenfelf-Tanenbaum Research Institute, Sinai Health System; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada., University of Toronto Musculoskeletal Oncology Unit, Sinai Health System; Department of Surgery, University of Toronto, Toronto, ON, Canada., Support Group for Children and Adolescents with Cancer (GRAACC), Pediatric Oncology Institute (IOP), Universidade Federal de Sao Paulo, Sao Paulo, Brail., The Jackson Laboratory, Farmington, CT 06032, USA., Molecular Pharmacology Branch, DCTD, NCI, NIH, Bethesda, MD 20892, USA., Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Genetics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: khanjav@mail.nih.gov.,
    1. Year: 2021
    2. Date: Nov 23
  2. Journal: Cell reports
    1. 37
    2. 8
    3. Pages: 110047
  4. Type of Article: Article
  5. Article Number: 110047
  6. ISSN: 2211-1247
  1. 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. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2021.110047
  3. PMID: 34818552
  4. View record in Web of Science®
  5. WOS: 000722838200001
  6. PII : S2211-1247(21)01533-3

Library Notes

  1. Fiscal Year: FY2021-2022
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