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000298953 245__ $$aCharacterization of single neurons reprogrammed by pancreatic cancer.
000298953 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2025
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000298953 520__ $$aThe peripheral nervous system (PNS) orchestrates organ function in health and disease. Most cancers including pancreatic ductal adenocarcinoma (PDAC) are infiltrated by PNS neurons, contributing to the complex tumor microenvironment (TME)1,2. However, neuronal cell bodies reside in various PNS ganglia, far from the tumor mass. Thus, cancer or healthy organ-innervating neurons elude current tissue sequencing datasets. To molecularly characterize pancreas- and PDAC-innervating neurons at single cell resolution, we developed 'Trace-n-seq'. This method employs retrograde tracing of axons from tissues to their respective ganglia followed by single-cell isolation and transcriptomic analysis. By characterizing >5.000 individual sympathetic and sensory neurons with about 4.000 innervating PDAC or healthy pancreas we reveal novel neuronal cell types and unique molecular networks distinct to pancreas, pancreatitis, PDAC, or melanoma metastasis. We integrate single-cell datasets of innervating neurons and the TME to establish a neuro-cancer-microenvironment interactome, delineate cancer-driven neuronal reprogramming and generate a pancreatic cancer-nerve signature. Pharmacological denervation induces a proinflammatory TME and increases immune-checkpoint inhibitor effectiveness. Nab-Paclitaxel causes intra-tumor neuropathy which attenuated PDAC growth and in combination with sympathetic denervation results in synergistic tumor regression. Our multi-dimensional data reveal new insights into the networks and functions of PDAC-innervating neurons, supporting inclusion of denervation in future therapies.
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000298953 7001_ $$0P:(DE-He78)59008c47a42b433b0328d0043b656ed2$$aRenders, Simon$$b1$$eFirst author$$udkfz
000298953 7001_ $$0P:(DE-He78)e0d709971755d81877e55f5dec9c4885$$aPanten, Jasper$$b2$$eFirst author
000298953 7001_ $$aDross, Nicolas$$b3
000298953 7001_ $$0P:(DE-He78)5b10e57ed1df98e2fd31edbdeed985ba$$aBauer, Katharina$$b4$$udkfz
000298953 7001_ $$0P:(DE-HGF)0$$aAzorin, Daniel$$b5
000298953 7001_ $$aHenriques, Vanessa$$b6
000298953 7001_ $$aVogel, Vanessa$$b7
000298953 7001_ $$0P:(DE-He78)0812f68beb25392984d3abbe3c58b6d2$$aKlein, Corinna$$b8
000298953 7001_ $$0P:(DE-He78)48b15f8f3a2bfd2cb3153cd0aa1d631f$$aLeppä, Aino-Maija$$b9$$udkfz
000298953 7001_ $$0P:(DE-He78)1c49297114e416ffcd8eb4adc965305d$$aBarriuso Ortega, Isabel$$b10
000298953 7001_ $$0P:(DE-He78)31d827eedcb4fc54aa6082c9026a2c23$$aSchwickert, Jonas$$b11
000298953 7001_ $$00000-0001-6783-5617$$aOurailidis, Iordanis$$b12
000298953 7001_ $$aMochayedi, Julian$$b13
000298953 7001_ $$0P:(DE-He78)697cb039ca08f3b7e5a2a52dbf020b46$$aMallm, Jan-Philipp$$b14$$udkfz
000298953 7001_ $$aMüller-Tidow, Carsten$$b15
000298953 7001_ $$00000-0002-9332-5749$$aMonyer, Hannah$$b16
000298953 7001_ $$00000-0002-6201-7399$$aNeoptolemos, John$$b17
000298953 7001_ $$00000-0002-7012-1196$$aHackert, Thilo$$b18
000298953 7001_ $$0P:(DE-He78)9aabcfee1a1fc9202398a45a63f0b1e3$$aStegle, Oliver$$b19$$udkfz
000298953 7001_ $$0P:(DE-He78)4c21317940f3ec566480ebcdcff3e00c$$aOdom, Duncan$$b20$$udkfz
000298953 7001_ $$0P:(DE-He78)81ae96953d6149e4307057d71a190019$$aOffringa, Rienk$$b21$$udkfz
000298953 7001_ $$00000-0003-1001-103X$$aStenzinger, Albrecht$$b22
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000298953 7001_ $$0P:(DE-He78)0f44fcb0b05507b0a20b175f7ba9ed1c$$aSprick, Martin$$b24$$udkfz
000298953 7001_ $$0P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aTrumpp, Andreas$$b25$$eLast author$$udkfz
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