Immuno-genomic landscape of osteosarcoma

Chia-Chin Wu, Hannah C. Beird, J. Andrew Livingston, Shailesh Advani, Akash Mitra, Shaolong Cao, Alexandre Reuben, Davis Ingram, Wei-Lien Wang, Zhenlin Ju, Cheuk Hong Leung, Heather Lin, Youyun Zheng, Jason Roszik, Wenyi Wang, Shreyaskumar Patel, Robert S. Benjamin, Neeta Somaiah, Anthony P. Conley, Gordon B. Mills, Patrick Hwu, Richard Gorlick, Alexander Lazar, Najat C. Daw, Valerae Lewis and P. Andrew Futreal ()
Additional contact information
Chia-Chin Wu: The University of Texas MD Anderson Cancer Center
Hannah C. Beird: The University of Texas MD Anderson Cancer Center
J. Andrew Livingston: The University of Texas MD Anderson Cancer Center
Shailesh Advani: The University of Texas MD Anderson Cancer Center
Akash Mitra: The University of Texas MD Anderson Cancer Center
Shaolong Cao: The University of Texas MD Anderson Cancer Center
Alexandre Reuben: The University of Texas MD Anderson Cancer Center
Davis Ingram: The University of Texas MD Anderson Cancer Center
Wei-Lien Wang: The University of Texas MD Anderson Cancer Center
Zhenlin Ju: The University of Texas MD Anderson Cancer Center
Cheuk Hong Leung: The University of Texas MD Anderson Cancer Center
Heather Lin: The University of Texas MD Anderson Cancer Center
Youyun Zheng: The University of Texas MD Anderson Cancer Center
Jason Roszik: The University of Texas MD Anderson Cancer Center
Wenyi Wang: The University of Texas MD Anderson Cancer Center
Shreyaskumar Patel: The University of Texas MD Anderson Cancer Center
Robert S. Benjamin: The University of Texas MD Anderson Cancer Center
Neeta Somaiah: The University of Texas MD Anderson Cancer Center
Anthony P. Conley: The University of Texas MD Anderson Cancer Center
Gordon B. Mills: The University of Texas MD Anderson Cancer Center
Patrick Hwu: The University of Texas MD Anderson Cancer Center
Richard Gorlick: The University of Texas MD Anderson Cancer Center
Alexander Lazar: The University of Texas MD Anderson Cancer Center
Najat C. Daw: The University of Texas MD Anderson Cancer Center
Valerae Lewis: The University of Texas MD Anderson Cancer Center
P. Andrew Futreal: The University of Texas MD Anderson Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-14646-w

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