Scholarlink

<p>The expression of Programmed Death-Ligand 1 (PD-L1) in tumor cells is regulated by multiple factors, and this expression further affects the immune function of the microenvironment. However, the effect of Interleukin 15 (IL-15) cytokine on PD-L1 expression in pancreatic cancer and its related mechanisms remain unclear. Bioinformatics databases suggest a close correlation between IL-15 and PD-L1. WB, qPCR, and flow cytometry experiments confirmed that IL-15 upregulates PD-L1 expression in pancreatic cancer cells. A co-culture model of pancreatic cancer cells and Peripheral Blood Mononuclear Cells (PBMCs) was established. Carboxyfluorescein Succinimidyl Ester (CFSE) labeling, intracellular flow cytometry staining, ELISA, and Lactate Dehydrogenase (LDH) release assay confirmed that IL-15 inhibits the proliferation, activation, cytokine secretion, and tumor-killing ability of CD8 + T cells in co-cultured PBMCs. Wound healing and Transwell assays showed that IL-15 enhances the migration and invasion abilities of pancreatic cancer cells in the co-culture system. However, PD-L1 neutralizing antibody (anti-PD-L1) reversed IL-15-induced immunosuppression, as well as the enhanced migration and invasion of pancreatic cancer cells caused by IL-15. Further WB experiments revealed that IL-15 upregulates PD-L1 expression in pancreatic cancer cells via the JAK1/STAT1/IRF1 axis, and Fludarabine reversed IL-15-induced immunosuppression and tumor migration/invasion. In animal experiments, immunofluorescence staining, in vivo small animal imaging, and HE staining demonstrated that IL-15 upregulates PD-L1 expression in pancreatic cancer, promotes tumor growth and metastasis, and inhibits tumor immune function. Thus, we conclude that IL-15 upregulates PD-L1 expression via the JAK1/STAT1/IRF1 axis, thereby promoting immune escape, invasion, and metastasis of pancreatic cancer.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

IL-15 promotes immune escape, invasion, and metastasis of pancreatic cancer by upregulating PD-L1 expression via the JAK1/STAT1/IRF1 pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月2日

查看全文
  • Jing Ning,
  • Xueyan Wei,
  • Huazhen Li,
  • Qing Li,
  • Haixing Jiang,
  • Xiubing Chen,
  • Weiwei Zhang

摘要

The expression of Programmed Death-Ligand 1 (PD-L1) in tumor cells is regulated by multiple factors, and this expression further affects the immune function of the microenvironment. However, the effect of Interleukin 15 (IL-15) cytokine on PD-L1 expression in pancreatic cancer and its related mechanisms remain unclear. Bioinformatics databases suggest a close correlation between IL-15 and PD-L1. WB, qPCR, and flow cytometry experiments confirmed that IL-15 upregulates PD-L1 expression in pancreatic cancer cells. A co-culture model of pancreatic cancer cells and Peripheral Blood Mononuclear Cells (PBMCs) was established. Carboxyfluorescein Succinimidyl Ester (CFSE) labeling, intracellular flow cytometry staining, ELISA, and Lactate Dehydrogenase (LDH) release assay confirmed that IL-15 inhibits the proliferation, activation, cytokine secretion, and tumor-killing ability of CD8 + T cells in co-cultured PBMCs. Wound healing and Transwell assays showed that IL-15 enhances the migration and invasion abilities of pancreatic cancer cells in the co-culture system. However, PD-L1 neutralizing antibody (anti-PD-L1) reversed IL-15-induced immunosuppression, as well as the enhanced migration and invasion of pancreatic cancer cells caused by IL-15. Further WB experiments revealed that IL-15 upregulates PD-L1 expression in pancreatic cancer cells via the JAK1/STAT1/IRF1 axis, and Fludarabine reversed IL-15-induced immunosuppression and tumor migration/invasion. In animal experiments, immunofluorescence staining, in vivo small animal imaging, and HE staining demonstrated that IL-15 upregulates PD-L1 expression in pancreatic cancer, promotes tumor growth and metastasis, and inhibits tumor immune function. Thus, we conclude that IL-15 upregulates PD-L1 expression via the JAK1/STAT1/IRF1 axis, thereby promoting immune escape, invasion, and metastasis of pancreatic cancer.