CD90 highly expressed population harbors a stemness signature and creates an immunosuppressive niche in pancreatic cancer. (1st July 2019)

• Record Type: Journal Article
• Authors: Shi, Juanjuan; Lu, Ping; Shen, Wenyan; He, Ruizhe; Yang, Min-Wei; Fang, Yuan; Sun, Yong-Wei; Niu, Ningning; Xue, Jing
• Is Part Of: Cancer letters. Volume 453(2019)
• Page Start: 158
• Page End: 169
• Publication Date: 2019-07-01
• Subjects: Pancreatic ductal adenocarcinoma (PDAC) -- CD90/Thy1 -- Stemness -- Monocyte/macrophage -- Immunosuppressive; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.03.051
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with no effective treatment. Cancer cells, especially cancer stem cells (CSCs), redirect immune cells to evade immune surveillance and even coopt these immune cells to support their growth and metastasis. However, the identification of CSCs and how CSCs interact with immune cells in PDAC remain uncharacterized. Here, we report that CD90 is expressed on both stromal and tumor cells and that high expression of CD90 is related to a poor prognosis in patients with PDAC. The CD90 highly expressed (CD90 hi ) population in PDAC cells harbors high stemness features and tumorigenicity. Notably, CD90 acts as an anchor for monocyte/macrophage adhesion, providing a physical interaction between CD90 hi cells and monocytes/macrophages. In response, the crosstalk between CD90 hi cells and monocytes/macrophages promotes immunosuppressive features of immune cells, which enhance the stemness and epithelial-mesenchymal transition (EMT) of PDAC cells. Moreover, PD-L1 is dominantly expressed in the CD90 hi population, providing another strategy for these cells to evade immune surveillance. These findings provide an understanding of the biological significance of CD90 expression in PDAC cells and uncover a novel mechanism for how "stem-like" PDAC cells evade immune surveillance. Highlights: The CD90 hi population harbors high stemness features in PDAC. CD90 bridges the crosstalk between pancreatic "stem-like" cells and surrounding monocytes/macrophages. Monocytes/macrophages promote the stemness and epithelial-mesenchymal transition (EMT) features of PDAC cells. The CD90 hi population expresses high PD-L1, providing another strategy for these cells to evade immune surveillance.