Recently, some monoclonal antibodies, such as those targeting CTLA-4, B7-H3, PD-1, and the PD-1 ligand PD-L1, have been designed to block immune checkpoints and have attracted much interest because of their satisfactory antitumor efficicacy.294–298 However, clinical trial results to date suggest that most checkpoint blockers are less effective in treating solid tumors, including osteosarcoma.275 The reason for this is not completely understood, and it is possible that T lymphocytes are not the main effector cells inhibiting osteosarcoma in humans. This evidence concerns the gene CTLA4 and osteosarcoma.