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@ARTICLE{Thiel:298953,
author = {V. Thiel$^*$ and S. Renders$^*$ and J. Panten$^*$ and N.
Dross and K. Bauer$^*$ and D. Azorin$^*$ and V. Henriques
and V. Vogel and C. Klein$^*$ and A.-M. Leppä$^*$ and I.
Barriuso Ortega$^*$ and J. Schwickert$^*$ and I. Ourailidis
and J. Mochayedi and J.-P. Mallm$^*$ and C. Müller-Tidow
and H. Monyer$^*$ and J. Neoptolemos and T. Hackert and O.
Stegle$^*$ and D. Odom$^*$ and R. Offringa$^*$ and A.
Stenzinger and F. Winkler$^*$ and M. Sprick$^*$ and A.
Trumpp$^*$},
title = {{C}haracterization of single neurons reprogrammed by
pancreatic cancer.},
journal = {Nature},
volume = {640},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2025-00387},
pages = {1042–1051},
year = {2025},
note = {#EA:A010#LA:A010# / 640, pages 1042–1051 (2025)},
abstract = {The 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.},
cin = {A010 / HD01 / A230 / B260 / B270 / D200 / B320 / W192},
ddc = {500},
cid = {I:(DE-He78)A010-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)A230-20160331 / I:(DE-He78)B260-20160331 /
I:(DE-He78)B270-20160331 / I:(DE-He78)D200-20160331 /
I:(DE-He78)B320-20160331 / I:(DE-He78)W192-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39961335},
doi = {10.1038/s41586-025-08735-3},
url = {https://inrepo02.dkfz.de/record/298953},
}