Endogenous Retrovirus Expression Distinguishes a Murine Osteosarcoma Model That Responds to Oncolytic Viroimmunotherapy Wedekind et al.
Description
Osteosarcoma remains one of the deadliest cancers in pediatrics and young adults, yet the utility of new cancer immunotherapies for osteosarcoma is largely unknown. We administered two types of immunotherapies, oncolytic virotherapy and immune checkpoint inhibition, alone and in combination, to two commonly used murine osteosarcoma models and observed divergent results. Mice bearing F420 showed no response, whereas those with K7M2 showed prolonged survival in response to combination therapy. To address model differences that underlie our observations, we found K7M2 had higher expression of immune-related genes and higher baseline immune cell infiltrates based on flow cytometry and RNA-seq deconvolution. While K7M2 harbored 12 fusion genes compared with none for F420, there were no significant differences in tumor mutational burden or predicted MHC class I binding of peptides derived from those or other nonsynonymous mutations. Instead, we found several mouse endogenous retrovirus sequences highly expressed in K7M2 compared with F420. Tetramer staining for one of them, gp70, was elevated in K7M2 but not F420, suggesting that endogenous retrovirus proteins are targets for the anti-tumor immune reaction. Given prior observations of endogenous retrovirus expression in human osteosarcomas, our findings may be translatable to human disease.