Autonomic modulation of the immune response and implications for CNS malignancies

While the central nervous system (CNS) has long been known to regulate global physiologic processes, its role in regulating immune responses has only relatively recently been appreciated. Specifically, CNS input via the autonomic nervous system (ANS) is increasingly emerging as a crucial modulator of immune responses in numerous pathologies, though understanding of the role of these pathways in malignancy is limited. Herein, we provide an overview of CNS-immune signaling pathways, outline the evidence of ANS inputs to immune organs, provide a detailed description of the impact of ANS signaling on immune cell functions, and consider the implications of ANS-immune regulation for the antitumor immune response and CNS inflammation, with a specific focus on how these factors coalesce to impact the antitumor immune response in intracranial malignancies. This review concludes by highlighting the need to better understand cancer neuro-immunology, the tripartite interactions of malignancy and immune cells within the unique niche of the nervous system.