Neuro-tumor interactions: Multi-dimensional mechanisms of neurotransmitter regulation in tumor immune evasion and metabolic reprogramming

Neurotransmitter-mediated regulation plays a multi-dimensional role in the tumor microenvironment, profoundly influencing key processes such as tumor immune evasion, metabolic reprogramming, and metastasis. However, the upstream regulatory mechanisms linking neural inputs to immune evasion and metabolic reprogramming remain incompletely understood. We systematically summarize current evidence from molecular, cellular, and immunological studies to elucidate how neurotransmitter-dependent mechanisms drive dynamic changes in the tumor microenvironment through the regulation of tumor cells and immune cells, and map the complex interaction networks between the nervous system and tumor progression. We propose a unifying "neuro-metabolic-immune axis" framework that highlights the dual role of neurotransmitters in suppressing anti-tumor immunity and facilitating tumor adaptation. By mapping this axis, we reveal new insights into tumor ecology and identify neural pathways as promising therapeutic targets. Targeting these pathways may enhance immunotherapy and disrupt tumor-supportive metabolism, offering new directions in precision oncology.