Neuroblastoma is one of the most common solid tumours occurring in childhood, and is responsible for about 15% of all paediatric cancer-related deaths. It either presents as a low-risk disease, which frequently shows spontaneous regression, or as high-risk disease, which often leads to death despite intensive multimodal therapies, with overall survival still below 50%. Hence, new treatment options are urgently needed.
Neuroblastoma is an immunologically cold tumour, with low mutational burden, few neo-antigens, limited cytotoxic T cell infiltration, and high amounts of infiltrating immunosuppressive cells. Accordingly, clinical studies applying checkpoint inhibitors have shown limited or no clinical response in neuroblastoma so far. The aim of my study is a deeper understanding of the immunological tumour microenvironement in neuroblastoma to foster the development and establishment of new combination immunotherapies that can convert cold tumours into hot tumours, taking into account the innate and the acquired immune system. To this end, I will examine novel treatment strategies combining checkpoint inhibitors and other agents in genetically engineered mouse models, and assess both treatment response and changes in the tumour microenvironement.