Characterization of pancreatic and biliary cancer stem cells in patient-derived tissue
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Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic cholangio-carcinoma (eCC) represent two cancer entities with devastating prognoses. Despite recent progress in research and treatment, therapy remains challenging. Cancer stem cells (CSCs) have been shown to play an important role in metastasis and chemoresistance. Therefore, CSCs may play a promising role as a potential therapeutic target.
A total of 31 patients (23 PDAC, 8 eCC) were included in the study. CSCs were analyzed in a single-cell suspension of tumor samples via fluorescence-activated cell scanning (FACS) with a functional Hoechst 33342 staining as well as a cell surface marker staining of the CSC-panel (CD24, CD44 and EpCAM) and markers to identify fibroblasts, leukocytes and components of the notch signaling pathway. Furthermore, the potential presence of CSCs among primary cancer-associated fibroblasts (CAFs) was assessed using the same FACS-panel.
We showed that CSCs are present in patient-derived dissociated tumor tissue. The functional and surface marker profile of CSC-detection did in fact correlate. The amount of CSCs was significantly correlated with tumor characteristics such as a higher UICC stadium and nodal invasion. CSCs were not restricted to the epithelial cell fraction in tumor tissues, which has been verified in independent analysis of primary cell cultures of CAFs.
Our study confirms the in vivo presence of CSCs in PDAC and eCC, stating a clinical significance thereof and thus their plausibility as therapeutic targets. In addition, stem-like cells also seem to constitute a part of the CAFs.

"Characterization of Pancreatic and Biliary Cancer Stem Cells in Patient-derived Tissue" was published in Anticancer Research. Authors are J. Gogolok, E. Seidel, A. Strönisch, A. Reutzel-Selke, I.M. Sauer, J. Pratschke, M. Bahra, and R.B. Schmuck.
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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.




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