Project description:
A research team from the Stem Cell Institute HI-STEM and the German Cancer Research Center (DKFZ), the Heidelberg University and international partner institutions, led by Prof. Andreas Trumpp and Dr. Vera Thiel, has developed a new method to characterize nerve cells that are reprogrammed by pancreatic cancer. The results were published in the journal Nature. All organs, including tumors, are penetrated and innervated by nerves. With the method “Trace-n-Seq,” it is now possible for the first time to identify and molecularly characterize, at the single-cell level, the neurons that innervate either healthy or cancerous pancreatic tissue. Using this approach, the researchers were able to identify new neuronal cell types and interaction networks and to create a “cancer–nerve signature profile” that characterizes tumor-induced neuronal reprogramming and its tumor-promoting effects.
Remarkably, targeted interruption of neural input generated a pro-inflammatory tumor microenvironment and significantly improved the efficacy of immune checkpoint therapies. Furthermore, chemotherapy with nab-paclitaxel not only inhibited tumor growth but also selectively reduced parts of the tumor–nerve network. These findings are now being translated into an early clinical trial to test whether denervation in combination with chemotherapy and checkpoint inhibitors is clinically effective. The results open new therapeutic avenues for pancreatic cancer, one of the most aggressive malignancies.
Publication:
Vera Thiel, Simon Renders, Jasper Panten, Nicolas Dross, Katharina Bauer, Daniel Azorin, Vanessa Henriques, Vanessa Vogel, Corinna Klein, Aino-Maija Leppä, Isabel Barriuso Ortega, Jonas Schwickert, Iordanis Ourailidis, Julian Mochayedi, Jan-Philipp Mallm, Carsten Müller-Tidow, Hannah Monyer, John Neoptolemos, Thilo Hackert, Oliver Stegle, Duncan T. Odom, Rienk Offringa, Albrecht Stenzinger, Frank Winkler, Martin Sprick, Andreas Trumpp. Characterization of single neurons reprogrammed by pancreatic cancer, Nature 2025
Submitting the Paper of the Month:
Else Kröner-Fresenius-Stiftung is using the series “Paper of the Month” to report in an exemplary and hot-off-the-press style on the outstanding work being done by the scientists it supports. We regularly present publications which have recently appeared in especially renowned journals, have emerged from foundation funding and been given appropriate acknowledgment. This is done in the respective categories “Original Paper” and “Review”. In the case of each of these publications, the first author and/or senior author are being funded by the foundation.
We invite all project managers, fellowship recipients and members of graduate study programs to send their work in accordance with the stated criteria as proposal for Paper of the Month to Ms. Anne Asschenfeldt (a.asschenfeldt@ekfs.de).
More Paper of the Month can be found here.
