TNF and osteosarcoma: In keeping with our observation that the anti-osteosarcoma potential of Smac mimetics hinges on the presence of TNFα produced by myeloid cells within the tumors, disaggregated cells from freshly-resected implanted tumors (consisting of both osteosarcoma and infiltrating non-cancerous cells) were efficiently killed in vitro by Smac mimetics as sole agents, whereas the corresponding in vitro-cultured osteosarcoma cells were only sensitive to Smac mimetics when co-treated with exogenous TNFα (Fig. 4e).