Osteosarcoma a cancer of bone is the third most common cancer in the adolescent population. Treatment incorporates aggressive surgery and intensive adjuvant chemotherapy. However the five-year survival of those with metastatic or recurrent disease is less than 25%, and has remained unchanged over the past 30 years. There is an urgent need to identify new therapeutic targets for the clinical management of osteosarcoma. We have established radiocarcinogen and syngeneic transplant mouse models of osteosarcoma in the laboratory. These immune competent models are being used to identify new genetic drivers of osteosarcoma development as well as to test the efficacy of immune targeted strategies in suppressing tumour growth. We are currently investigating the role of inflammatory cytokines as well as checkpoint inhibitors as potential therapeutic targets in osteosarcoma. We identified interleukin 23 (IL23), an inflammatory cytokine, as a potential therapeutic target in osteosarcoma. Our interest in IL23 is reinforced by the recent genome wide association study, where GRM4 (Glutamate metabotropic receptor 4) gene at 6p21.3 (rs1906953) was identified as having the strongest association with genetic susceptibility to osteosarcoma in humans⁽²⁾. GRM4 activation has been associated with autoimmune diseases through suppression of inflammatory cytokines, including IL23⁽³⁾. In this talk I will discuss our findings exploring the link between IL23 and GRM4 in cancer development and identify novel treatments options that may have utility in the treatment of osteosarcoma.