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Immuno-genomic landscape of osteosarcoma.
Wu, Chia-Chin; Beird, Hannah C; Andrew Livingston, J; Advani, Shailesh; Mitra, Akash; Cao, Shaolong; Reuben, Alexandre; Ingram, Davis; Wang, Wei-Lien; Ju, Zhenlin; Hong Leung, Cheuk; Lin, Heather; Zheng, Youyun; Roszik, Jason; Wang, Wenyi; Patel, Shreyaskumar; Benjamin, Robert S; Somaiah, Neeta; Conley, Anthony P; Mills, Gordon B; Hwu, Patrick; Gorlick, Richard; Lazar, Alexander; Daw, Najat C; Lewis, Valerae; Futreal, P Andrew.
Affiliation
  • Wu CC; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Beird HC; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Andrew Livingston J; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Advani S; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Mitra A; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Cao S; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Reuben A; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Ingram D; Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wang WL; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Ju Z; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Hong Leung C; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Lin H; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Zheng Y; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Roszik J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wang W; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Patel S; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Benjamin RS; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Somaiah N; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Conley AP; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Mills GB; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Hwu P; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Gorlick R; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Lazar A; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Daw NC; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Lewis V; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Futreal PA; Department of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nat Commun ; 11(1): 1008, 2020 02 21.
Article in En | MEDLINE | ID: mdl-32081846
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Neoplasms / Osteosarcoma Type of study: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limits: Adolescent / Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Neoplasms / Osteosarcoma Type of study: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limits: Adolescent / Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Type: Article Affiliation country: United States