Immuno-genomic landscape of osteosarcoma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 02 2020
21 02 2020
Historique:
received:
10
12
2018
accepted:
20
01
2020
entrez:
22
2
2020
pubmed:
23
2
2020
medline:
6
5
2020
Statut:
epublish
Résumé
Limited clinical activity has been seen in osteosarcoma (OS) patients treated with immune checkpoint inhibitors (ICI). To gain insights into the immunogenic potential of these tumors, we conducted whole genome, RNA, and T-cell receptor sequencing, immunohistochemistry and reverse phase protein array profiling (RPPA) on OS specimens from 48 pediatric and adult patients with primary, relapsed, and metastatic OS. Median immune infiltrate level was lower than in other tumor types where ICI are effective, with concomitant low T-cell receptor clonalities. Neoantigen expression in OS was lacking and significantly associated with high levels of nonsense-mediated decay (NMD). Samples with low immune infiltrate had higher number of deleted genes while those with high immune infiltrate expressed higher levels of adaptive resistance pathways. PARP2 expression levels were significantly negatively associated with the immune infiltrate. Together, these data reveal multiple immunosuppressive features of OS and suggest immunotherapeutic opportunities in OS patients.
Identifiants
pubmed: 32081846
doi: 10.1038/s41467-020-14646-w
pii: 10.1038/s41467-020-14646-w
pmc: PMC7035358
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1008Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA183793
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA221675
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217842
Pays : United States
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