TGFB1 and neoplasm: Bone metastases drive systemic immunosuppression through a self-perpetuating"vicious cycle"[25, 26]: Tumor cells in bone secrete cytokines (IL-1, IL-6, and TNF-α) that activate osteoclasts, disrupting bone homeostasis and releasing pro-tumor factors (TGF-β, and IGF) that further fuel tumor growth and reshape the microenvironment.