Neuron-tumor communication in solid tumors: from bona fide synapses to pseudo-synaptic neural interfaces

Neuron-tumor communication is emerging as a distinct layer of tumor-host interaction beyond conventional stromal, vascular, and immune regulation. Recent studies show that malignant cells can detect neuronal activity and convert neural signals into growth-promoting cellular responses. In the brain, glioma cells can become electrically integrated into neuronal circuits, where glutamatergic input drives depolarization, calcium influx, and downstream signaling. In extracranial tumors, neural influence appears more heterogeneous, involving spatially organized neurochemical niches, receptor-enriched cancer-nerve contacts ('pseudo-synapses'), autonomic pathways, and injury-associated neuroimmune remodeling. These findings raise important questions about how neural input regulates tumor cell state, metabolism, immune tone, and therapeutic adaptation. This review evaluates the evidence linking neural activity to cancer progression across anatomical contexts and outlines the experimental standards needed to distinguish structured neuron-tumor interfaces from broader neural effects within the tumor microenvironment.