To our knowledge, although a recent preclinical study using anti-PD-L1 and anti-CTLA-4 antibodies demonstrated good control of metastatic osteosarcoma [32], our present data provide the first direct evidence that the combination effect of anti-PD-L1 and anti-CTLA-4 antibodies with X-ray is the best therapeutic strategy for both the primary tumor and distant tumors or metastases in osteosarcoma. This evidence concerns the gene CTLA4 and osteosarcoma.