Lymphocyte-targeted immune therapies with check-point inhibitors (anti-PD1/PDL1) were disappointing in refractory/relapsed osteosarcoma phase I/II trials with the majority of the patients experiencing progressive disease when anti-PD1/PDL1 was given either as single agent46,47 or combined with metronomic cyclophosphamide48. This evidence concerns the gene CD274 and osteosarcoma.