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A local sympathetic-immune axis inhibits melanoma growth in mice by dictating adrenergic control

GSE295045 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2026/04/06 Platform GPL24247
Summary
The nervous system drives tumor growth directly through intra-tumoral axons and indirectly through the systemic action of hormones. Yet contexts where the nervous system inhibits tumor growth are less defined. Here, we performed optical reconstruction of axonal innervation in mouse models of cutaneous melanoma, revealing progressive innervation by sympathetic axons. Local depletion of these axons accelerates while local optogenetic activation slows melanoma growth, together consistent with these axons acting as a physiological growth brake. The sympathetic nervous system is typically associated with driving tumor growth through activation of β adrenergic receptors (ARs). Here we find that the initial tumor seeding conditions sensitizes melanomas from β AR driven growth promotion towards a2 AR driven growth inhibition. Mechanistically, axonal activation of a2 ARs restricts the number and distribution of pro-tumor myeloid cells, independent of T cell activity. Together, our data reveal context-dependent, bidirectional neural control of tumor progression.
Published in
A local sympathetic-immune axis inhibits melanoma growth in mice by dictating adrenergic control
Liu T, Kutsovsky DY, Earlie EM et al. · Neuron 2026 · PMID 42061411 · doi:10.1016/j.neuron.2026.04.016
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Also filed as BioProject PRJNA1252704 and SRA study SRP579719. Searching any of these in the dataset finder brings you back here.

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