Nerve Fibers in the Tumor Microenvironment are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer

• Main Authors: Lara R. Heij, Xiuxiang Tan, Jakob N. Kather, Jan M. Niehues, Shivan Sivakumar, Nicole Heussen, Gregory van der Kroft, Steven W. M. Olde Damink, Sven Lang, Merel R. Aberle, Tom Luedde, Nadine T. Gaisa, Jan Bednarsch, Drolaiz H. W. Liu, Jack P. M. Cleutjens, Dominik P. Modest, Ulf P. Neumann, Georg J. Wiltberger
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Journal of Clinical Medicine
• Subjects: tumor microenvironment; machine learning; nerve fiber density; spatial arrangements; tertiary lymphoid structures; pancreatic cancer
• Online Access: https://www.mdpi.com/2077-0383/10/3/490

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 crosstalk 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.