Surface and global proteomics identify ROR2 and other proteins as potentially actionable immunotherapeutic targets in osteosarcoma

Osteosarcoma (OS) is the most common human primary bone cancer, primarily affecting children and young adults. While the survival rate of patients diagnosed with localized OS is ∼65%, this decreases to ∼20% for patients with metastatic disease, and recurrent disease remains largely incurable. Therefore, identifying new therapeutic strategies is urgently needed for metastatic and refractory OS. This study analyzes the surfaceomes and global proteomes of 22 unique OS patient-derived xenografts (PDXs) using mass spectrometry to identify surface proteins for potential immunotherapeutic targeting. Both methods identify known OS-associated surface candidates including LRRC15, MMP14, MRC2, and CADM1, and several poorly characterized targets, including ROR2 and TMEM119. Both ROR2 and TMEM119 display robust expression in OS tissues but only limited or no expression in normal pediatric tissues, and loss of both targets reduces the migration of OS cells. These data provide a resource of surface proteins as potential immunotherapeutic targets in OS.