Immuno-genomic landscape of osteosarcoma

Osteosarcoma Cells

Source: NCI Center for Cancer Research \ Creator: Michael Blank, Ying Zhang

Wu CC, Beird HC, Andrew Livingston J, Advani S, Mitra A, Cao S, Reuben A, Ingram D, Wang WL, Ju Z, Hong Leung C, Lin H, Zheng Y, Roszik J, Wang W, Patel S, Benjamin RS, Somaiah N, Conley AP, Mills GB, Hwu P, Gorlick R, Lazar A, Daw NC, Lewis V, Futreal PA.

Nat Commun.

February 21, 2020

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.

Program:
CTD²
Last updated: July 29, 2020