Immuno-genomic landscape of osteosarcoma

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 R. 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 Görlick(The University of Texas MD Anderson Cancer Center), Alexander J. Lazar(The University of Texas MD Anderson Cancer Center), Najat C. Daw(The University of Texas MD Anderson Cancer Center), Valerae O. Lewis(The University of Texas MD Anderson Cancer Center), P. Andrew Futreal(The University of Texas MD Anderson Cancer Center)
Nature Communications
February 21, 2020
10.1038/s41467-020-14646-w
Cited by 243Open Access
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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.

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