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Article

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

1
Department of General, Gastrointestinal, Hepatobiliary and Transplant Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany
2
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands
3
Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany
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Department of Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany
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Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK
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Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK
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Department of Medical Statistics, RWTH Aachen University, 52074 Aachen, Germany
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Center of Biostatistics and Epidemiology, Medical School, Sigmund Freud University, 1020 Vienna, Austria
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Department of Surgery, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
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Department of Pathology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
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CARIM Cardiovascular Research Institute Maastricht, Maastricht University, 6229 HX Maastricht, The Netherlands
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Department of Hematology, Oncology and Tumor Immunology, CVK, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
*
Author to whom correspondence should be addressed.
Georg J. Wiltberger and Ulf P. Neumann contributed equally to this work.
Academic Editor: Maria Del Pilar Acedo Nunez
J. Clin. Med. 2021, 10(3), 490; https://doi.org/10.3390/jcm10030490
Received: 3 January 2021 / Revised: 18 January 2021 / Accepted: 20 January 2021 / Published: 30 January 2021
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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. View Full-Text
Keywords: tumor microenvironment; machine learning; nerve fiber density; spatial arrangements; tertiary lymphoid structures; pancreatic cancer tumor microenvironment; machine learning; nerve fiber density; spatial arrangements; tertiary lymphoid structures; pancreatic cancer
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MDPI and ACS Style

Heij, L.R.; Tan, X.; Kather, J.N.; Niehues, J.M.; Sivakumar, S.; Heussen, N.; van der Kroft, G.; Damink, S.W.M.O.; Lang, S.; Aberle, M.R.; Luedde, T.; Gaisa, N.T.; Bednarsch, J.; Liu, D.H.W.; Cleutjens, J.P.M.; Modest, D.P.; Neumann, U.P.; Wiltberger, G.J. Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer. J. Clin. Med. 2021, 10, 490. https://doi.org/10.3390/jcm10030490

AMA Style

Heij LR, Tan X, Kather JN, Niehues JM, Sivakumar S, Heussen N, van der Kroft G, Damink SWMO, Lang S, Aberle MR, Luedde T, Gaisa NT, Bednarsch J, Liu DHW, Cleutjens JPM, Modest DP, Neumann UP, Wiltberger GJ. Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer. Journal of Clinical Medicine. 2021; 10(3):490. https://doi.org/10.3390/jcm10030490

Chicago/Turabian Style

Heij, Lara R., Xiuxiang Tan, Jakob N. Kather, Jan M. Niehues, Shivan Sivakumar, Nicole Heussen, Gregory van der Kroft, Steven W.M.O. 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, and Georg J. Wiltberger 2021. "Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer" Journal of Clinical Medicine 10, no. 3: 490. https://doi.org/10.3390/jcm10030490

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