Neurotransmitters: Key regulators of the tumor immune microenvironment

Recent studies have revealed that neurotransmitters, as a class of important signaling molecules, have functional roles that extend beyond the traditional nervous system and play critical regulatory functions in the tumor immune microenvironment. Research has demonstrated that various classical neurotransmitters and their receptors are widely expressed in tumor tissues. Through complex receptor-mediated signaling networks, neurotransmitters dynamically regulate the functions of diverse cell types, including tumor cells and immune cells, thereby influencing tumor progression. Based on these discoveries, significant progress has been made in developing innovative drugs targeting neurotransmitter-receptor axes. Multiple agents, such as N-methyl-D-aspartate receptor (NMDAR), γ-aminobutyric acid-A (GABA-A) agonists, and dopamine receptor antagonists, have demonstrated promising antitumor effects in both preclinical studies and clinical trials. This review systematically summarizes the multidimensional regulatory mechanisms of neurotransmitters in tumor immunity and comprehensively discusses recent advances in neurotransmitter-targeted therapies. These findings not only provide a theoretical foundation for developing novel immunotherapeutic strategies based on neurotransmitter modulation but also open new research perspectives for understanding the emerging field of "neuro-immune-tumor" crosstalk.