The microarchitecture of pancreatic cancer as measured by diffusion-weighted magnetic resonance imaging is altered by T cells with a tumor promoting Th17 phenotype
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 diffu...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
5 January 2020
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| In: |
International journal of molecular sciences
Year: 2020, Volume: 21, Issue: 1, Pages: 1-16 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21010346 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/ijms21010346 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1422-0067/21/1/346 
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| Author Notes: | Philipp Mayer, Alica Linnebacher, Hannah Glennemeier-Marke, Nicole Marnet, Frank Bergmann, Thilo Hackert, Miriam Klauss, Tanja Poth and Matthias M. Gaida |
| Summary: | 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. |
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| Item Description: | Gesehen am 31.03.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21010346 |