Nerve fibers in the tumor microenvironment are co-localized with lymphoid aggregates in pancreatic cancer

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Lara R. Heij - , RWTH Aachen University, Maastricht University (Author)
  • Xiuxiang Tan - , RWTH Aachen University, Maastricht University (Author)
  • Jakob N. Kather - , RWTH Aachen University (Author)
  • Jan M. Niehues - , RWTH Aachen University (Author)
  • Shivan Sivakumar - , University of Oxford (Author)
  • Nicole Heussen - , RWTH Aachen University, Sigmund Freud Private University (Author)
  • Gregory van der Kroft - , RWTH Aachen University (Author)
  • Steven W.M. Olde Damink - , RWTH Aachen University, Maastricht University, Maastricht University Medical Centre (UMC+) (Author)
  • Sven Lang - , RWTH Aachen University (Author)
  • Merel R. Aberle - , RWTH Aachen University, Maastricht University (Author)
  • Tom Luedde - , RWTH Aachen University (Author)
  • Nadine T. Gaisa - , RWTH Aachen University (Author)
  • Jan Bednarsch - , RWTH Aachen University (Author)
  • Drolaiz H.W. Liu - , Maastricht University Medical Centre (UMC+) (Author)
  • Jack P.M. Cleutjens - , Maastricht University Medical Centre (UMC+), Maastricht University (Author)
  • Dominik P. Modest - , Charité – Universitätsmedizin Berlin (Author)
  • Ulf P. Neumann - , RWTH Aachen University, Maastricht University Medical Centre (UMC+) (Author)
  • Georg J. Wiltberger - , RWTH Aachen University (Author)

Abstract

B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome. The desmoplastic stroma is a complex system in which cross-talk takes place between cancer-associated fibroblasts, immune cells and cancer cells. Indirect and direct cellular interactions within the tumor microenvironment (TME) drive key processes such as tumor progression, metastasis formation and treatment resistance. In order to understand the aggressiveness of PDAC and its resistance to therapeutics, the TME needs to be further unraveled. There are some limited data about the influence of nerve fibers on cancer progression. Here we show that small nerve fibers are located at lymphoid aggregates in PDAC. This unravels future pathways and has potential to improve clinical outcome by a rational development of new therapeutic strategies.

Details

Original languageEnglish
Article number490
Pages (from-to)1-12
Number of pages12
JournalJournal of clinical medicine
Volume10
Issue number3
Publication statusPublished - 1 Feb 2021
Peer-reviewedYes
Externally publishedYes

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • Machine learning, Nerve fiber density, Pancreatic cancer, Spatial arrangements, Tertiary lymphoid structures, Tumor microenvironment