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Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer
SIMPLE SUMMARY: The excessive desmoplasia is the hallmark of human pancreatic cancer that influences the local T-cell-based immune response. In the present work, the stromal collagen organization in normal and malignant pancreatic tissues as well as its relationsship to T-cell distribution in pancre...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344977/ https://www.ncbi.nlm.nih.gov/pubmed/34359549 http://dx.doi.org/10.3390/cancers13153648 |
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author | Kamionka, Eva-Maria Qian, Baifeng Gross, Wolfgang Bergmann, Frank Hackert, Thilo Beretta, Carlo A. Dross, Nicolas Ryschich, Eduard |
author_facet | Kamionka, Eva-Maria Qian, Baifeng Gross, Wolfgang Bergmann, Frank Hackert, Thilo Beretta, Carlo A. Dross, Nicolas Ryschich, Eduard |
author_sort | Kamionka, Eva-Maria |
collection | PubMed |
description | SIMPLE SUMMARY: The excessive desmoplasia is the hallmark of human pancreatic cancer that influences the local T-cell-based immune response. In the present work, the stromal collagen organization in normal and malignant pancreatic tissues as well as its relationsship to T-cell distribution in pancreatic cancer were studied. It was found that differences in collagen organization do not change the spatial orientation of T-cell migration and do not influence the availability of tumor cells for T-cells. The results of the study do not support the concept of use of stroma collagen organization for improvement of spatial T-cell distribution in the tumor. ABSTRACT: The dominant intrastromal T-cell infiltration in pancreatic cancer is mainly caused by the contact guidance through the excessive desmoplastic reaction and could represent one of the obstacles to an effective immune response in this tumor type. This study analyzed the collagen organization in normal and malignant pancreatic tissues as well as its influence on T-cell distribution in pancreatic cancer. Human pancreatic tissue was analyzed using immunofluorescence staining and multiphoton and SHG microscopy supported by multistep image processing. The influence of collagen alignment on activated T-cells was studied using 3D matrices and time-lapse microscopy. It was found that the stroma of malignant and normal pancreatic tissues was characterized by complex individual organization. T-cells were heterogeneously distributed in pancreatic cancer and there was no relationship between T-cell distribution and collagen organization. There was a difference in the angular orientation of collagen alignment in the peritumoral and tumor-cell-distant stroma regions in the pancreatic ductal adenocarcinoma tissue, but there was no correlation in the T-cell densities between these regions. The grade of collagen alignment did not influence the directionality of T-cell migration in the 3D collagen matrix. It can be concluded that differences in collagen organization do not change the spatial orientation of T-cell migration or influence stromal T-cell distribution in human pancreatic cancer. The results of the present study do not support the rationale of remodeling of stroma collagen organization for improvement of T-cell–tumor cell contact in pancreatic ductal adenocarcinoma. |
format | Online Article Text |
id | pubmed-8344977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83449772021-08-07 Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer Kamionka, Eva-Maria Qian, Baifeng Gross, Wolfgang Bergmann, Frank Hackert, Thilo Beretta, Carlo A. Dross, Nicolas Ryschich, Eduard Cancers (Basel) Article SIMPLE SUMMARY: The excessive desmoplasia is the hallmark of human pancreatic cancer that influences the local T-cell-based immune response. In the present work, the stromal collagen organization in normal and malignant pancreatic tissues as well as its relationsship to T-cell distribution in pancreatic cancer were studied. It was found that differences in collagen organization do not change the spatial orientation of T-cell migration and do not influence the availability of tumor cells for T-cells. The results of the study do not support the concept of use of stroma collagen organization for improvement of spatial T-cell distribution in the tumor. ABSTRACT: The dominant intrastromal T-cell infiltration in pancreatic cancer is mainly caused by the contact guidance through the excessive desmoplastic reaction and could represent one of the obstacles to an effective immune response in this tumor type. This study analyzed the collagen organization in normal and malignant pancreatic tissues as well as its influence on T-cell distribution in pancreatic cancer. Human pancreatic tissue was analyzed using immunofluorescence staining and multiphoton and SHG microscopy supported by multistep image processing. The influence of collagen alignment on activated T-cells was studied using 3D matrices and time-lapse microscopy. It was found that the stroma of malignant and normal pancreatic tissues was characterized by complex individual organization. T-cells were heterogeneously distributed in pancreatic cancer and there was no relationship between T-cell distribution and collagen organization. There was a difference in the angular orientation of collagen alignment in the peritumoral and tumor-cell-distant stroma regions in the pancreatic ductal adenocarcinoma tissue, but there was no correlation in the T-cell densities between these regions. The grade of collagen alignment did not influence the directionality of T-cell migration in the 3D collagen matrix. It can be concluded that differences in collagen organization do not change the spatial orientation of T-cell migration or influence stromal T-cell distribution in human pancreatic cancer. The results of the present study do not support the rationale of remodeling of stroma collagen organization for improvement of T-cell–tumor cell contact in pancreatic ductal adenocarcinoma. MDPI 2021-07-21 /pmc/articles/PMC8344977/ /pubmed/34359549 http://dx.doi.org/10.3390/cancers13153648 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kamionka, Eva-Maria Qian, Baifeng Gross, Wolfgang Bergmann, Frank Hackert, Thilo Beretta, Carlo A. Dross, Nicolas Ryschich, Eduard Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer |
title | Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer |
title_full | Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer |
title_fullStr | Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer |
title_full_unstemmed | Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer |
title_short | Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer |
title_sort | collagen organization does not influence t-cell distribution in stroma of human pancreatic cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344977/ https://www.ncbi.nlm.nih.gov/pubmed/34359549 http://dx.doi.org/10.3390/cancers13153648 |
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