Harnessing the nervous system to overcome resistance to immunotherapy in oral cancer

The long-term goal is to elucidate reciprocal nerve-cancer signals that drive cancer progression. Aim 1 will determine the mechanisms by which neuron-dependent cancer cell signaling regulates cytotoxic T-cell function, utilizing pharmacological and genetic approaches combined with advanced spatial imaging techniques in syngeneic mouse models. Aim 2 will identify the extracellular vesicle-shuttled driver miRNAs of TAN reprogramming and their roles in oral cancer progression, using human-derived sensory neurons and functional genomic approaches. The project seeks to understand how reprogrammed TANs induce a maladaptive immune response that supports tumor progression and therapy resistance, ultimately paving the way for treatment strategies targeting neuronal mechanisms of immunosuppression.