Abstract
Abstract
The nervous system is a key regulator of cancer immunity, influencing tumor development and treatment response through neuroimmune interactions. Both peripheral and central circuits transmit neural signals that directly influence immune cell recruitment, activation, and effector function within the tumor microenvironment. Evidences indicate that sympathetic, parasympathetic, sensory neurons, and glial cells actively reshape the immune landscape through neurotransmitters and neuromodulators. Central neural circuits, such as catecholaminergic and stress-responsive pathways, further integrate psychological states and autonomic outflow to systemically reprogram immunity. However, how these diverse neural signals converge with tumor and immune cell interactions remains poorly defined. This Review synthesizes current advances across four dimensions: the roles of peripheral neurons and central neural circuits in cancer immunity; glial cell contributions to immunosuppression and tumor progression; reciprocal influences of tumor cells on neural remodeling; and neuron-independent neural signaling through immune-expressed adrenergic, cholinergic, and peptidergic receptors. We highlight that perineural invasion, tumor innervation heterogeneity, and receptor subtype-specific signaling are key factors in immune evasion and resistance to immune checkpoint inhibitor. By integrating these perspectives, this Review establishes the nervous system as a critical yet underexplored dimension of cancer immunology and proposes that context-defined and receptor-specific modulation of selected neuroimmune pathways may enhance immunotherapy.