| Literature DB >> 31285612 |
Atsunori Kamiya1,2,3, Yohsuke Hayama4, Shigeki Kato5, Akihiko Shimomura6, Takushi Shimomura7,8, Katsumasa Irie7, Ryosuke Kaneko9, Yuchio Yanagawa9, Kazuto Kobayashi5, Takahiro Ochiya10,11.
Abstract
The effects of autonomic innervation of tumors on tumor growth remain unclear. Here we developed a series of genetic techniques to manipulate autonomic innervation in a tumor- and fiber-type-specific manner in mice with human breast cancer xenografts and in rats with chemically induced breast tumors. Breast cancer growth and progression were accelerated following stimulation of sympathetic nerves in tumors, but were reduced following stimulation of parasympathetic nerves. Tumor-specific sympathetic denervation suppressed tumor growth and downregulated the expression of immune checkpoint molecules (programed death-1 (PD-1), programed death ligand-1 (PD-L1), and FOXP3) to a greater extent than with pharmacological α- or β-adrenergic receptor blockers. Genetically induced simulation of parasympathetic innervation of tumors decreased PD-1 and PD-L1 expression. In humans, a retrospective analysis of breast cancer specimens from 29 patients revealed that increased sympathetic and decreased parasympathetic nerve density in tumors were associated with poor clinical outcomes and correlated with higher expression of immune checkpoint molecules. These findings suggest that autonomic innervation of tumors regulates breast cancer progression.Entities:
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Year: 2019 PMID： 31285612 DOI： 10.1038/s41593-019-0430-3
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884