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This graphical abstract illustrates the multidimensional crosstalk between neurons and tumor microenvironment as well as targeted intervention strategies identified in the study. It highlights three core interaction axes: nerve-tumor crosstalk mediated by neurotransmitters and neurotrophic factors, neuro-vascular communication driving angiogenesis via Norepinephrine/β2-Adrenergic Receptor/Vascular Endothelial Growth Factor signaling, and neuro-immune regulation involving Myeloid-Derived Suppressor Cells and M2 macrophage polarization. The central panel reveals the key mechanism: psychological stress activates sympathetic nerves, which downregulates tumor cell AlkB Homolog 5 via NE/Adrenoceptor Beta 2, leading to m6A-RNA packaging into extracellular vesicles that promote neural overactivation. The right and bottom panels present effective interventions, including radiotherapy + perampanel, fisetin (inhibiting extracellular vesicles uptake), Glial Cell Line-Derived Neurotrophic Factor-neutralizing antibody, and sympathetic denervation, which collectively suppress tumor progression and metastasis.
Wu et al. (Mon,) studied this question.