CTLA4 and osteosarcoma: Recently, emerging evidence has shown that the expression level of PD-1 on CD8-positive TILs is greatly reduced after treatment with an anti-PD-L1 antibody, while the expression of CTLA-4 is increased in a metastatic osteosarcoma mouse model, indicating that PD-L1 and CTLA-4 may have complementary roles in inhibiting CD8+ CTL-induced antitumor immunity.368 These results provide enthusiasm for immunotherapy studies and the use of combination approaches.