As we said above, mutations in TP53, RB1, and ATRX genes can promote the growth, invasion, and metastasis of osteosarcoma, which is a kind of ‘cold tumor’, and the microenvironment of osteosarcoma can monitor the tumor well, and it is less responsive to immune checkpoint blockade, which is confirmed by the calculation of the TIDE score, so the effect of high TMB on osteosarcoma is more inclined to promote the development of osteosarcoma, resulting in a poorer prognosis of osteosarcoma patients with high TMB. This evidence concerns the gene TP53 and osteosarcoma.