TMIC-59. ENTANGLED: THE INTERPLAY OF CELLULAR PLASTICITY AND NEURONAL SIGNALING IN BRAIN CANCER PROGRESSION

Abstract The interplay between two recently proposed hallmarks of cancer, namely dedifferentiation/transdifferentiation and altered neuronal signaling, may dictate the spatiotemporal coupling between neurons and astrocytes. Synaptic activity correlates with brain cancer progression and further influences the directionality of metabolites. Through phenotypic plasticity, brain parenchymal cells may dedifferentiate in a manner that determines the directionality of metabolites, thereby altering plasticity and exerting selective pressure on the immune microenvironment within the brain. Therapeutic advancements in brain cancers, including maximizing surgical resection margins and Chimeric Antigen Receptor (CAR) T-cell therapy, have their own limitations. Thus, understanding the interplay between dedifferentiation/transdifferentiation and its role in dictating altered neuronal signaling to modulate the brain tumor microenvironment may provide novel targets for improving prognosis and limiting therapeutic toxicity.