Journal
CANCER LETTERS
Volume 453, Issue -, Pages 158-169Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.03.051
Keywords
Pancreatic ductal adenocarcinoma (PDAC); CD90/Thy1; Stemness; Monocyte/macrophage; Immunosuppressive
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Funding
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning [TP2015007]
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20161312]
- National Natural Science Foundation of China [81702938, 81770628]
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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 sternness 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.
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