@article{405e216b99cb46ef831c28a14ff0895a,
title = "Immuno-genomic landscape of osteosarcoma",
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.",
author = "Wu, {Chia Chin} and Beird, {Hannah C.} and {Andrew Livingston}, J. and Shailesh Advani and Akash Mitra and Shaolong Cao and Alexandre Reuben and Davis Ingram and Wang, {Wei Lien} and Zhenlin Ju and {Hong Leung}, Cheuk and Heather Lin and Youyun Zheng and Jason Roszik and Wenyi Wang and Shreyaskumar Patel and Benjamin, {Robert S.} and Neeta Somaiah and Conley, {Anthony P.} and Mills, {Gordon B.} and Patrick Hwu and Richard Gorlick and Alexander Lazar and Daw, {Najat C.} and Valerae Lewis and Futreal, {P. Andrew}",
note = "Funding Information: Sequencing support was provided by Cancer Genomics Laboratories and Baylor Human Genome Center. Bioinformatics pipeline support was provided by John Zhang, Chang-Jiun Wu, and Xingzhi Song. Alijunaid Alhussain and Ruth Alejo Salazar conducted immunos-taining scoring. The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/. We graciously acknowledge International Cancer Genome Consortium (ICGC), The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) (https://ocg. cancer.gov/programs/target), including specimen donors and research groups for their work. This work was supported by Triumph Over Kid Cancer Foundation (to V.L)., A Shelter for Cancer Families (ASCF), formerly Amshwand Sarcoma Cancer Foundation (to the Sarcoma Oncology Group), QuadW Foundation (to the Sarcoma Oncology Group), Cancer Prevention Research Institute of Texas (R120501 to P.A.F., RP170067 to A.M. and Y.Z.), and Welch Foundation{\textquoteright}s Robert A. Welch Distinguished University Chair Award (G-0040 to P.A.F.). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-14646-w",
language = "English (US)",
volume = "11",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}