Based on these perspectives, the present study is aimed to determine: (1) the expression profile of PD-L1 in most prevalent primary bone tumors, (2) the expression level of IFN-γ, as a well-described modulator of PD-L1: PD-1 checkpoint, (3) the circulating level of TGF- β in primary bone tumors; (4) the association of PD-L1, IFN-γ, and TGF- β aberrant expression with primary bone tumor severity, metastasis and recurrence; and (5) the relevance of PD-L1, IFN-γ and TGF- β expression profile with the status of CD4/CD8 in patients with malignant and benign bone tumors. This evidence concerns the gene IFNG and bone benign neoplasm.