期刊
FASEB JOURNAL
卷 34, 期 6, 页码 8442-8458出版社
WILEY
DOI: 10.1096/fj.201902186R
关键词
apoptosis; endoplasmic reticulum stress; exosomes; p38 MAPK; pancreatic cancer; T lymphocytes
资金
- Major Research Project of Science Technology, Department of Zhejiang Province [2019C03048]
- National Natural Science Foundation of China [817, 02358]
- Medical Science and Technology of Zhejiang Province [WKJ-ZJ-1824]
- Zhejiang Traditional Chinese Medicine Research Fund Program [2019ZB071]
Pancreatic cancer is the fourth most lethal malignancy and is characterized by poor immunogenicity. Pancreatic cancer cells have various strategies to suppress host immune response, evade immune defenses, and facilitate tumor growth and development. As a mode of long-range intercellular communication, cancer-derived exosomes contribute to impairment of the immune system. However, the mechanisms that induce changes in the activities of signal transduction pathways in immune cells, which are influenced by tumor-derived exosomes, are poorly understood. We (1) treated peripheral T lymphocytes with pancreatic cancer-derived exosomes, tagged CD63 with tdTomato, to trace exosome transfer from pancreatic cancer cells to T lymphocytes; (2) carried out a cytotoxicity assay of exosome-treated T lymphocytes using the Real Time Cellular Analysis system; (3) performed RNA sequencing and gene set enrichment analysis to explore the pivotal signaling pathway that mediates apoptosis in exosome-treated T lymphocytes; and (4) demonstrated the role of p38 mitogen-activated protein kinase (MAPK) and endoplasmic reticulum (ER) stress in exosome-induced T-lymphocyte apoptosis. In conclusion, these results indicate that pancreatic cancer cells secrete exosomes, which are taken up by T lymphocytes to activate p38 MAPK, and then induce ER stress-mediated apoptosis, ultimately causing immunosuppression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据