Taken together,these data support the idea that immunoselection of K7M2 metastatic osteosarcoma cells that eventually cause lethal disease in α-PD-L1 mAb treated mice evokes an adaptive resistance mechanism in the microenvironment, and instead the tumor or tumor microenvironment may be using CTLA-4 ligation as an alternative pathway to escape immune destruction. This evidence concerns the gene CTLA4 and osteosarcoma.