Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

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

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

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

Permalink

Publisher:: Elsevier BV
Publication Type:: Journal Article
Citation:: Cell Rep, 2021, 37, (8), pp. 110047
Issue Date:: 2021-11-23

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download Accepted versionAdobe PDF (2.74 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Brohl, AS
dc.contributor.author	Sindiri, S
dc.contributor.author	Wei, JS
dc.contributor.author	Milewski, D
dc.contributor.author	Chou, H-C
dc.contributor.author	Song, YK
dc.contributor.author	Wen, X
dc.contributor.author	Kumar, J
dc.contributor.author	Reardon, HV
dc.contributor.author	Mudunuri, US
dc.contributor.author	Collins, JR
dc.contributor.author	Nagaraj, S
dc.contributor.author	Gangalapudi, V
dc.contributor.author	Tyagi, M
dc.contributor.author	Zhu, YJ
dc.contributor.author	Masih, KE
dc.contributor.author	Yohe, ME
dc.contributor.author	Shern, JF
dc.contributor.author	Qi, Y
dc.contributor.author	Guha, U
dc.contributor.author	Catchpoole, D
dc.contributor.author	Orentas, RJ
dc.contributor.author	Kuznetsov, IB
dc.contributor.author	Llosa, NJ
dc.contributor.author	Ligon, JA
dc.contributor.author	Turpin, BK
dc.contributor.author	Leino, DG
dc.contributor.author	Iwata, S
dc.contributor.author	Andrulis, IL
dc.contributor.author	Wunder, JS
dc.contributor.author	Toledo, SRC
dc.contributor.author	Meltzer, PS
dc.contributor.author	Lau, C
dc.contributor.author	Teicher, BA
dc.contributor.author	Magnan, H
dc.contributor.author	Ladanyi, M
dc.contributor.author	Khan, J
dc.date.accessioned	2022-04-11T04:30:57Z
dc.date.available	2021-11-01
dc.date.available	2022-04-11T04:30:57Z
dc.date.issued	2021-11-23
dc.identifier.citation	Cell Rep, 2021, 37, (8), pp. 110047
dc.identifier.issn	2211-1247
dc.identifier.issn	2211-1247
dc.identifier.uri	http://hdl.handle.net/10453/156052
dc.description.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.
dc.format	Print
dc.language	eng
dc.publisher	Elsevier BV
dc.relation.ispartof	Cell Rep
dc.relation.isbasedon	10.1016/j.celrep.2021.110047
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1116 Medical Physiology
dc.subject.mesh	Adolescent
dc.subject.mesh	Antigens, Neoplasm
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Child
dc.subject.mesh	Child, Preschool
dc.subject.mesh	Female
dc.subject.mesh	Gene Expression
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Humans
dc.subject.mesh	Immune Checkpoint Proteins
dc.subject.mesh	Immunogenetics
dc.subject.mesh	Immunotherapy, Adoptive
dc.subject.mesh	Infant
dc.subject.mesh	Lymphocytes, Tumor-Infiltrating
dc.subject.mesh	Male
dc.subject.mesh	Neoplasms
dc.subject.mesh	Receptors, Antigen, T-Cell
dc.subject.mesh	Transcriptome
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Whole Exome Sequencing
dc.subject.mesh	Lymphocytes, Tumor-Infiltrating
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Humans
dc.subject.mesh	Neoplasms
dc.subject.mesh	Receptors, Antigen, T-Cell
dc.subject.mesh	Antigens, Neoplasm
dc.subject.mesh	Immunotherapy, Adoptive
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Immunogenetics
dc.subject.mesh	Gene Expression
dc.subject.mesh	Adolescent
dc.subject.mesh	Child
dc.subject.mesh	Child, Preschool
dc.subject.mesh	Infant
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Transcriptome
dc.subject.mesh	Whole Exome Sequencing
dc.subject.mesh	Immune Checkpoint Proteins
dc.title	Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.
dc.type	Journal Article
utslib.citation.volume	37
utslib.location.activity	United States
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1116 Medical Physiology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
utslib.copyright.status	open_access	*
dc.date.updated	2022-04-11T04:30:52Z
pubs.issue	8
pubs.publication-status	Published
pubs.volume	37
utslib.citation.issue	8

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/156052