Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer

• DOI: 10.1038/s41467-022-29659-w
• Publication Date: 2022-04-13T10:14:25Z
• Authors: Jérémy Guillot; Chloé Dominici; Adrien Lucchesi; Huyen Thi Trang N...; Angélique Puget; Mélanie Hocine; Martha M. Rangel-...; Milesa Simic; Jérémy Nigri; Fabienne Guillaumond; Martin Bigonnet; Nelson Dusetti; Jimmy Perrot; Jonathan Lopez; Anders Etzerodt; Toby Lawrence; Pierre Pudlo; Florence Hubert; Jean-Yves Scoazec; Serge A. van de P...; Richard Tomasini; Sophie Chauvet; Fanny Mann
• Keywords: Sprouting

Abstract Neuronal nerve processes in the tumor microenvironment were highlighted recently. However, origin of intra-tumoral nerves remains poorly known, part because technical difficulties tracing fibers via conventional histological preparations. Here, we employ three-dimensional (3D) imaging cleared tissues for a comprehensive analysis sympathetic innervation murine model pancreatic ductal adenocarcinoma (PDAC). Our results support two independent, but coexisting, mechanisms: passive engulfment pre-existing within tumors plus an active, localized sprouting axon terminals into non-neoplastic lesions and periphery. Ablation innervating increases growth spread. This effect is explained by observation that sympathectomy intratumoral CD163 + macrophage numbers, which contribute to worse outcome. Altogether, our findings provide insights mechanisms nervous system exerts cancer-protective properties mouse PDAC.