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Article

The Microarchitecture of Pancreatic Cancer as Measured by Diffusion-Weighted Magnetic Resonance Imaging Is Altered by T Cells with a Tumor Promoting Th17 Phenotype

1
Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, 69120 Heidelberg, Germany
2
Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
3
Institute of Pathology, University Medical Center Mainz, JGU-Mainz, 55131 Mainz, Germany
4
Clinical Pathology, Klinikum Darmstadt GmbH, 64283 Darmstadt, Germany
5
Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
6
Research Center for Immunotherapy, University Medical Center Mainz, JGU-Mainz, 55131 Mainz, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(1), 346; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010346
Received: 16 December 2019 / Revised: 2 January 2020 / Accepted: 3 January 2020 / Published: 5 January 2020
(This article belongs to the Special Issue Basic and Translational Models of Cooperative Oncogenesis)
Diffusion-weighted magnetic resonance imaging (DW-MRI) is a diagnostic tool that is increasingly used for the detection and characterization of focal masses in the abdomen, among these, pancreatic ductal adenocarcinoma (PDAC). DW-MRI reflects the microarchitecture of the tissue, and changes in diffusion, which are reflected by changes in the apparent diffusion coefficient (ADC), are mainly attributed to variations in cellular density, glandular formation, and fibrosis. When analyzing the T cell infiltrates, we found an association of a tumor-promoting subpopulation, characterized by the expression of interleukin (IL) 21 and IL26, with high ADC values. Moreover, the presence of IL21+ and IL26+ positive T cells was associated with poor prognosis. Pancreatic cancers—but not healthy pancreatic tissue—expressed receptors for IL21 and IL26, a finding that could be confirmed in pancreatic cell lines. The functionality of these receptors was demonstrated in pancreatic tumor cell lines, which showed phosphorylation of ERK1/2 and STAT3 pathways in response to the respective recombinant interleukins. Moreover, in vitro data showed an increased colony formation of tumor cells. In summary, our data showed an association of IL21+ and IL26+ immune cell infiltration, increased ADC, and aggressive tumor disease, most likely due to the activation of the key cancer signaling pathways ERK1/2 and STAT3 and formation of tumor colonies. View Full-Text
Keywords: pancreatic cancer; tumor microenvironment; IL21; IL26; DW-MRI; ADC pancreatic cancer; tumor microenvironment; IL21; IL26; DW-MRI; ADC
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MDPI and ACS Style

Mayer, P.; Linnebacher, A.; Glennemeier-Marke, H.; Marnet, N.; Bergmann, F.; Hackert, T.; Klauss, M.; Poth, T.; Gaida, M.M. The Microarchitecture of Pancreatic Cancer as Measured by Diffusion-Weighted Magnetic Resonance Imaging Is Altered by T Cells with a Tumor Promoting Th17 Phenotype. Int. J. Mol. Sci. 2020, 21, 346. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010346

AMA Style

Mayer P, Linnebacher A, Glennemeier-Marke H, Marnet N, Bergmann F, Hackert T, Klauss M, Poth T, Gaida MM. The Microarchitecture of Pancreatic Cancer as Measured by Diffusion-Weighted Magnetic Resonance Imaging Is Altered by T Cells with a Tumor Promoting Th17 Phenotype. International Journal of Molecular Sciences. 2020; 21(1):346. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010346

Chicago/Turabian Style

Mayer, Philipp, Alica Linnebacher, Hannah Glennemeier-Marke, Nicole Marnet, Frank Bergmann, Thilo Hackert, Miriam Klauss, Tanja Poth, and Matthias M. Gaida 2020. "The Microarchitecture of Pancreatic Cancer as Measured by Diffusion-Weighted Magnetic Resonance Imaging Is Altered by T Cells with a Tumor Promoting Th17 Phenotype" International Journal of Molecular Sciences 21, no. 1: 346. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010346

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