CLASSIFYING IMMUNE DISPOSITION IN NEUROBLASTOMA USING OPTICAL MICROSCOPY TECHNIQUES AND GENE EXPRESSION PROFILING

Neuroblastoma, the most common extracranial solid tumor in children, is a complex and challenging disease. The recent removal of the IVS (4S) category from clinical practice has left a crucial gap in our understanding of this unique subtype, particularly its remarkable ability to regress spontaneously. This thesis embarks on a journey to uncover the secrets of the tumor microenvironment (TME) in Neuroblastoma, using cutting-edge spatial immunofluorescence and RNA sequencing to explore how these tumors interact with their surroundings. Our research reveals a surprising truth: IVS Neuroblastoma, long thought to be driven by the immune system, is actually steered by different forces. The spontaneous regression seen in these cases isn’t due to immune activity but rather to the activation of apoptosis and ferroptosis pathways—cell death mechanisms that seem to hold the key to why these tumors sometimes just disappear on their own. At the heart of this thesis is the role of MYCN, a powerful oncogene that shapes the TME in profound ways. When MYCN is amplified, it pushes the tumor into a more aggressive, dangerous state, leading to poorer outcomes for patients. But in MYCN non-amplified tumors, there’s a different story—one where the presence of immune cells in the TME is associated with better survival, offering hope and a potential path to less aggressive disease. This research not only redefines our understanding of IVS Neuroblastoma but also highlights the critical influence of MYCN on the tumor’s microenvironment. The discoveries made here pave the way for new approaches to treatment and better tools for predicting patient outcomes, offering hope for more effective strategies in combating this challenging disease.