Endogenous Retrovirus Expression Distinguishes a Murine Osteosarcoma Model That Responds to Oncolytic Viroimmunotherapy Wedekind et al.

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.