We searched PubMed and ClinicalTrials.gov (2010-June 2025) using ‘osteosarcoma’, ‘neurotrophin/NGF/BDNF/RET/Trk’, and ‘immunity’; English; prioritised primary OS data then mechanistic studies in other tumours; excluded reviews/abstract-only reports; key outcomes included pathway activity, immune metrics, and clinical responses. The gene discussed is RET; the disease is osteosarcoma.