| First Author | Yu J | Year | 2026 |
| Journal | Neuron | PubMed ID | 41856110 |
| Mgi Jnum | J:383222 | Mgi Id | MGI:8323314 |
| Doi | 10.1016/j.neuron.2026.02.028 | Citation | Yu J, et al. (2026) 6-Hydroxydopamine promotes antitumor immunity through macrophage remodeling beyond sympathetic ablation. Neuron |
| abstractText | The sympathetic nervous system has emerged as a critical regulator of cancer progression, yet the underlying mechanisms remain unclear. Here, we compare genetic, pharmacological (6-hydroxydopamine [6-OHDA]), and surgical denervation in mouse breast cancer models. While all methods deplete sympathetic nerves, only 6-OHDA suppresses tumor growth, revealing a disconnect between sympathetic ablation and antitumor effect. Mechanistic investigations reveal that 6-OHDA suppresses tumor growth through immune activation rather than sympathetic ablation. 6-OHDA induces cancer cell interferon (IFN)-beta production, which promotes monocyte differentiation into pro-inflammatory macrophages characterized by interferon-stimulated gene (ISG) expression. These ISG(+) macrophages are essential for the expansion of type 1 T helper (T(H)1) cells, which mediate prolonged tumor suppression. By contrast, sympathetic ablation alone does not affect macrophage differentiation or tumor growth. Our findings uncover an immunomodulatory function of 6-OHDA beyond its established neurotoxic activity and suggest the therapeutic potential of harnessing the macrophage-T(H)1 axis for breast cancer. |
