Unfortunately, despite high PD-L1 expression levels (ranging from 14 to 75%) and promising results in preclinical models [19,20], immune checkpoint inhibitors in unselected patients with relapsed osteosarcoma have shown very limited clinical activity, with an overall response rate (ORR) of <10% (e.g., 4.5% with pembrolizumab in the SARC028 trial [21] and 6.7% with pembrolizumab plus metronomic cyclophosphamide in the PEMBROSARC trial) [22]. The gene discussed is CD274; the disease is osteosarcoma.