التفاصيل البيبلوغرافية
| العنوان: |
Immuno-transcriptomic profiling of extracranial pediatric solid malignancies. |
| المؤلفون: |
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 S., Collins, Jack R., Nagaraj, Sushma, Gangalapudi, Vineela, Tyagi, Manoj, Zhu, Yuelin J., Masih, Katherine E., Yohe, Marielle E., Shern, Jack F., Qi, Yue, Guha, Udayan |
| المصدر: |
Cell Reports; Nov2021, Vol. 37 Issue 8, pN.PAG-N.PAG, 1p |
| مستخلص: |
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. [Display omitted] • We describe the immunogenomics landscape of 14 pediatric extracranial solid tumors • Immunophenotype is prognostic of survival in neuroblastoma and osteosarcoma • We identify multiple targets for immune therapy • Immune targeting of PRAME demonstrates in vitro and in vivo cytotoxicity Brohl et al. perform immunogenomics analysis of a cohort of 788 pediatric extracranial solid tumors and cell lines, representing 14 diagnoses, utilizing RNA sequencing. They broadly describe prognostically relevant immunophenotypes and provide proof of concept of a transcriptomics-informed adoptive cellular therapy approach, validating PRAME as a multi-pediatric cancer immunotherapy target. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
