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Immuno-transcriptomic profiling of extracranial pediatric solid malignancies

Cell Rep. 2021-11; 
Andrew S Brohl, Sivasish Sindiri, Jun S Wei, David Milewski, Hsien-Chao Chou, Young K Song, Xinyu Wen, Jeetendra Kumar, Hue V Reardon, Uma S Mudunuri, Jack R Collins, Sushma Nagaraj, Vineela Gangalapudi, Manoj Tyagi, Yuelin J Zhu, Katherine E Masih, Marielle E Yohe, Jack F Shern, Yue Qi, Udayan Guha, Daniel Catchpoole, Rimas J Orentas, Igor B Kuznetsov, Nicolas J Llosa, John A Ligon, Brian K Turpin, Daniel G Leino, Shintaro Iwata, Irene L Andrulis, Jay S Wunder, Silvia R C Toledo, Paul S Meltzer, Ching Lau, Beverly A Teicher, Heather Magnan, Marc Ladanyi, Javed Khan
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摘要

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 ce... More

关键词

PRAME, RNA sequencing, T cell receptor, adoptive cell therapy, immunogenomics, immunopeptidomics, pediatric oncology, tumor-infiltrating lymphocytes
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