LPS, similarly, is classified as Tier 3: despite its dose-dependent TLR4 activation (100 ng/kg body weight enhances CD8+ T cell infiltration in osteosarcoma; 206), the risk of sepsis at therapeutic doses (≥5 μg per mouse causes 40% murine mortality; 209) and individual variations in human TLR4 polymorphisms (220) present severe challenges to its clinical translation. The gene discussed is TLR4; the disease is osteosarcoma.