Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2022

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

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Fanny Mann
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  • PersonId : 997576
  • IdHAL : fanny-mann

Abstract

Neuronal nerve processes in the tumor microenvironment were highlighted recently. However, the origin of intra-tumoral nerves remains poorly known, in part because of technical difficulties in tracing nerve fibers via conventional histological preparations. Here, we employ three-dimensional (3D) imaging of cleared tissues for a comprehensive analysis of sympathetic innervation in a murine model of pancreatic ductal adenocarcinoma (PDAC). Our results support two independent, but coexisting, mechanisms: passive engulfment of preexisting sympathetic nerves within tumors plus an active, localized sprouting of axon terminals into non-neoplastic lesions and tumor periphery. Ablation of the innervating sympathetic nerves increases tumor growth and spread. This effect is explained by the observation that sympathectomy increases intratumoral CD163 + macrophage numbers, which contribute to the worse outcome. Altogether, our findings provide insights into the mechanisms by which the sympathetic nervous system exerts cancer-protective properties in a mouse model of PDAC.
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hal-03794776 , version 1 (03-10-2022)

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Attribution - CC BY 4.0

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Jérémy Guillot, Chloé Dominici, Adrien Lucchesi, Huyen Thi Trang Nguyen, Angélique Puget, et al.. Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer. Nature Communications, 2022, 13, ⟨10.1038/s41467-022-29659-w⟩. ⟨hal-03794776⟩
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