Further, the pro-tumor cytokines and chemokines we detect (TNF, CCL20 and MMP19) are coherent with models in which osteosarcoma cell-derived exosomes or TIM-3-related cargo drive macrophages toward M2 states, thereby amplifying invasive and immunosuppressive circuits; experimental disruption of such signaling impairs metastatic competence in osteosarcoma models (44). This evidence concerns the gene TNF and osteosarcoma.