The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
Use the dropdown menu or ‘Previous’ and ‘Next’ buttons to navigate the list.
Thiel, V., Renders, S., Panten, J. et al. Nature. 640: 1042–1051. (2025).
doi: 10.1038/s41586-025-08735-3.
doi: 10.1038/s41586-025-08735-3.
Summary of the findings
Summary of the findingsThe peripheral nervous system (PNS) plays a critical role in pancreatic cancer biology, but its molecular interaction with tumors has remained largely unexplored due to the distant location of neuronal cell bodies from the tumor mass. We developed a method called Trace-n-Seq, which combines retrograde axonal tracing with single-cell RNA sequencing, enabling for the first time the molecular characterization of tumor-innervating neurons. By profiling over 5,000 individual neurons from healthy and pancreatic ductal adenocarcinoma (PDAC) tissue, we discovered that PDAC induces profound transcriptional reprogramming in sympathetic and sensory neurons, including the emergence of a distinct “cancer nerve signature.” These reprogrammed neurons engage in active crosstalk with cancer-associated fibroblasts and tumor cells, promoting tumor progression. Importantly, disrupting these neuronal inputs via pharmacological or surgical denervation sensitized tumors to immune-checkpoint inhibitors and reduced tumor growth. We also found that the widely used chemotherapy agent nab-paclitaxel inhibits mostly sensory neurons in PDAC innervating nerves which contributes to its therapeutic efficacy. Our study uncovers an unexpected, yet targetable dimension of the tumor microenvironment—cancer-induced neuronal remodeling.
.
Future impact
Our findings open new avenues for targeting the neural component innervating and promoting pancreatic cancer. Denervation strategies could be integrated into combination therapies to enhance the efficacy of immunotherapies and chemotherapy. Furthermore, the cancer nerve signature may serve as a diagnostic or prognostic biomarker. The Trace-n-Seq method can be broadly applied to study neuro-immune interactions in other solid tumors or diseases involving peripheral nerve innervation.
.
