| Title: |
Immuno-transcriptomic profiling of extracranial pediatric solid malignancies. |
| Authors: |
Brohl, AS; Sindiri, S; Wei, JS; Milewski, D; Chou, H-C; Song, YK; Wen, X; Kumar, J; Reardon, HV; Mudunuri, US; Collins, JR; Nagaraj, S; Gangalapudi, V; Tyagi, M; Zhu, YJ; Masih, KE; Yohe, ME; Shern, JF; Qi, Y; Guha, U; Catchpoole, D; Orentas, RJ; Kuznetsov, IB; Llosa, NJ; Ligon, JA; Turpin, BK; Leino, DG; Iwata, S; Andrulis, IL; Wunder, JS; Toledo, SRC; Meltzer, PS; Lau, C; Teicher, BA; Magnan, H; Ladanyi, M; Khan, J |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2022 |
| Collection: |
University of Technology Sydney: OPUS - Open Publications of UTS Scholars |
| Subject Terms: |
0601 Biochemistry and Cell Biology; 1116 Medical Physiology; Adolescent; Antigens; Neoplasm; Cell Line; Tumor; Child; Preschool; Female; Gene Expression; Gene Expression Profiling; Humans; Immune Checkpoint Proteins; Immunogenetics; Immunotherapy; Adoptive; Infant; Lymphocytes; Tumor-Infiltrating; Male; Neoplasms; Receptors; Antigen; T-Cell; Transcriptome; Tumor Microenvironment; Whole Exome Sequencing |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print; application/pdf |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
Cell Rep; Cell Rep, 2021, 37, (8), pp. 110047; http://hdl.handle.net/10453/156052 |
| Availability: |
http://hdl.handle.net/10453/156052 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.FE2B566F |
| Database: |
BASE |