Neural regulation in cancer: A comprehensive review from tumorigenesis and progression to immune evasion

Scientific tradition long treated neural and immune activities as essentially separate domains. Contrary to this historical view, studies from the past several decades have fundamentally transformed our understanding. Across various cancers, the nervous system establishes a dynamic, bidirectional regulatory network connecting neural elements, tumors, and immune cells. This occurs through direct interactions (including paracrine communication and electrochemical neuron-cancer signaling) and indirect mechanisms involving the tumor microenvironment (TME) regulation. A two-way regulatory relationship characterizes the nervous system-tumor interaction, combining neural control of oncogenesis with tumor-driven neural plasticity to form a pathological feedback loop. Our analysis delves into how the central nervous system (CNS) and the peripheral nervous system (PNS) directly regulate tumor behavior and anti-tumor immunity, and how cancers hijack normal neural signaling pathways to promote growth and immune evasion. We further examine how tumors and anticancer treatments reciprocally affect neural functionality and immune homeostasis.