Kamionka Eva-Maria, Qian Baifeng, Gross Wolfgang, Bergmann Frank, Hackert Thilo, Beretta Carlo A, Dross Nicolas, Ryschich Eduard
Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 365/420, 69120 Heidelberg, Germany.
Department of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Cancers (Basel). 2021 Jul 21;13(15):3648. doi: 10.3390/cancers13153648.
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.
胰腺癌中主要的基质内T细胞浸润主要是由过度的促结缔组织增生反应导致的接触引导引起的，这可能是这种肿瘤类型中有效免疫反应的障碍之一。本研究分析了正常和恶性胰腺组织中的胶原组织及其对胰腺癌中T细胞分布的影响。使用免疫荧光染色以及多光子和二次谐波产生显微镜，并辅以多步图像处理来分析人类胰腺组织。使用三维基质和延时显微镜研究胶原排列对活化T细胞的影响。研究发现，恶性和正常胰腺组织的基质具有复杂的个体组织结构。T细胞在胰腺癌中分布不均，且T细胞分布与胶原组织之间没有关系。在胰腺导管腺癌组织中，肿瘤周围和远离肿瘤细胞的基质区域的胶原排列角度方向存在差异，但这些区域之间的T细胞密度没有相关性。胶原排列程度不影响T细胞在三维胶原基质中的迁移方向。可以得出结论，胶原组织的差异不会改变T细胞迁移的空间方向，也不会影响人类胰腺癌中基质T细胞的分布。本研究结果不支持为改善胰腺导管腺癌中T细胞与肿瘤细胞接触而重塑基质胶原组织的理论依据。
