Interactions among bone, immune, and tumor cells sustain the vicious cycle of bone metastasis. Tumor cells release cytokines that activate T cells to produce proosteoclastogenic factors, such as RANKL, which activate OCs. In turn, the release of bone matrix growth factors during bone resorption enhances the tumor growth. MDSCs originate from BM and migrate to secondary lymphoid organs where they inhibit the antitumor immune response mediated by CD8 T cells. Consequently, the increased tumor growth induces the production of osteolytic factors which activates the OCs, the cells responsible for bone destruction.