کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10914639 | 1088803 | 2014 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
L1CAM promotes enrichment of immunosuppressive T cells in human pancreatic cancer correlating with malignant progression
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کلمات کلیدی
TGF-β1PBMCT-regsPDACPancreatic adenocarcinoma - آدنوکارسینوم پانکراسPancreatic ductal adenocarcinoma - آدنوکارسینوم پانکراس داکتالTumor stroma - استروما تومورperipheral blood mononuclear cells - سلول های تک هسته ای خون محیطیRegulatory T cells - سلولهای تی تنظیمکنندهImmune evasion - فرار از ایمنchronic pancreatitis - پانکراتیت مزمنMalignant progression - پیشرفت بدخیم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Regulatory T cell (T-reg) enrichment in the tumor microenvironment is regarded as an important mechanism of tumor immune escape. Hence, the presence of T-regs in highly malignant pancreatic ductal adenocarcinoma (PDAC) is correlated with short survival. Likewise, the adhesion molecule L1CAM is upregulated during PDAC progression in the pancreatic ductal epithelium also being associated with poor prognosis. To investigate whether L1CAM contributes to enrichment of T-regs in PDAC, human CD4+CD25+CD127âCD49dâ T-regs and CD4+CD25â T-effector cells (T-effs) were isolated by magnetic bead separation from blood of healthy donors. Their phenotype and functional behavior were analyzed in dependence on human premalignant (H6c7) or malignant (Panc1) pancreatic ductal epithelial cells, either exhibiting or lacking L1CAM expression. T cells derived from blood and tumors of PDAC patients were analyzed by flow cytometry and findings were correlated with clinical parameters. Predominantly T-regs but not T-effs showed an increased migration on L1CAM expressing H6c7 and Panc1 cells. Whereas proliferation of T-regs did not change in the presence of L1CAM, T-effs proliferated less, exhibited a decreased CD25 expression and an increased expression of CD69. Moreover, these T-effs exhibited a regulatory phenotype as they inhibited proliferation of autologous T cells. Accordingly, CD4+CD25âCD69+ T cells were highly abundant in PDAC tissues compared to blood being associated with nodal invasion and higher grading in PDAC patients. Overall, these data point to an important role of L1CAM in the enrichment of immunosuppressive T cells in particular of a CD4+CD25âCD69+-phenotype in PDAC providing a novel mechanism of tumor immune escape which contributes to tumor progression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Oncology - Volume 8, Issue 5, July 2014, Pages 982-997
Journal: Molecular Oncology - Volume 8, Issue 5, July 2014, Pages 982-997
نویسندگان
Evelin Grage-Griebenow, Elfi Jerg, Artur Gorys, Daniel Wicklein, Daniela Wesch, Sandra Freitag-Wolf, Lisa Goebel, Ilka Vogel, Thomas Becker, Michael Ebsen, Christoph Röcken, Peter Altevogt, Udo Schumacher, Heiner Schäfer, Susanne Sebens,