Neural Control Loops in Cancer: From Central Circuits to Local Tumor–Nerve–Immune Ecosystems

Cancer is increasingly recognized as an innervated, electrically responsive disease governed by bidirectional interactions between tumors and the nervous system. Within peripheral tumors, autonomic and sensory fibers release neurotransmitters and neuropeptides, while cancer, stromal, immune, and Schwann cells remodel nerves through trophic, guidance, and inflammatory signals. In the central nervous system (CNS), neuronal activity supports glioma growth through activity-dependent mitogens and functional synapses. At the organismal level, stress, inflammation, cachexia, and treatment toxicity engage brain–body circuits that reshape tumor metabolism and immunity. This review organizes these interactions into five modules: central circuit control, autonomic efferents, sensory and nociceptive signaling, neuron–glioma synapses, and local nerve–Schwann–stromal–immune ecosystems. We distinguish human evidence from causal animal and cell model findings, examine perineural invasion as an active multicellular program, and explain context-dependent adrenergic and cholinergic effects. We further assess therapeutic opportunities, including receptor-selective neuromodulation, blockade of trophic and neuroimmune pathways, and combinations with immunotherapy or cytotoxic treatment. Translation will require spatially resolved human validation, longitudinal measures of neural activity, and interventions that preserve essential neural function.