Glioblastoma (GB) is an aggressive and immunosuppressed brain tumor with few therapeutic options. The development of novel therapies requires a better understanding of the bi-directional communication between the tumor and the surrounding brain parenchyma. On one hand, soluble factors released by GB cells alter the balance of inhibitory and excitatory neurotransmission, and disrupt neural circuits; on the other, recent findings suggest that neuronal stimuli modulate brain microenvironment with effects on tumor growth. Here, we will use mouse models of GB to examine glioma-induced plastic reorganizations in peritumoral areas. Importantly, we will investigate the effect of neurotransmission on tumor growth focusing on GABAergic and dopaminergic transmission.
We will also investigate the role of microglia in modulating the neuron-neuron synaptic contacts and the recently identified neuron-glioma synapses. The role of cannabinoid system in modulating glioma growth and its interaction with microglia and infiltrating macrophage will be also investigated. For this study we will combine different expertise in the field of oncology, immunology, and neuroscience, to dissect neural-immune-cancer interactions and identify novel antineoplastic strategies. Altogether, this project will shed new light on the interactions among neurons, tumor cells, glial cells and infiltrating immune cells, leading to the identification of novel cellular and molecular therapeutic targets and to the validation of non-invasive glioma therapies.