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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},
}