The combination of unique mouse models of gliomas reflecting human pathology with high-dimensional technologies (spatial transcriptomics, immunocytochemistry and intravital imaging) will be explored in order to identify myeloid and lymphoid subsets with their unique transcriptional profiles and localization in the microenvironment of gliomas. One of the most important impediments to understand cancer invasion is the inability to acquire direct observations of the invasion process in vivo. Taking advantage of animals grafted with fluorescent tumor cells we can address the dynamics of interactions occurring between glioma cells, neurons and vasculature which can be visualized by intravital two-photon microscopy during the progression of the disease. Also, the role of immune cells and tumor vessel kinetics can offer strategies for vascular normalization in orchestration with immune checkpoint inhibitors (CPI)-based treatments. The possibility to image a tumor at microscopic resolution in a minimally compromised cerebral environment represents an improvement of current GBM animal models which should benefit the field of neuro-oncology and drug testing. To improve immunotherapy, it is essential to determine the molecular mechanisms that mediate GBM to escape. Our vision is that this project will broaden our understanding of anti-tumor immune responses under specific neuro-oncological conditions and enable the identification of molecules that are being dysregulated. This knowledge may allow novel diagnostics and therapeutic options that can potentially be tailored to patients.