| First Author | Liu T | Year | 2026 |
| Journal | Neuron | Volume | 114 |
| Issue | 9 | Pages | 1576-1593.e8 |
| PubMed ID | 42061411 | Mgi Jnum | J:384830 |
| Mgi Id | MGI:8329314 | Doi | 10.1016/j.neuron.2026.04.016 |
| Citation | Liu T, et al. (2026) A local sympathetic-immune axis inhibits melanoma growth in mice by dictating adrenergic control. Neuron |
| abstractText | 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 beta-adrenergic receptors (ARs). Here, we find that the initial tumor seeding conditions sensitize melanomas from betaAR-driven growth promotion toward alpha2-AR-driven growth inhibition. Mechanistically, the axonal activation of alpha2 ARs restricts the number and distribution of pro-tumor myeloid cells, independently of T cell activity. Together, our data reveal context-dependent, bidirectional neural control of tumor progression. |
