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  • br Conflict of interest br None br Authors

    2020-08-30


    Conflict of interest
    None.
    Authors contribution
    AT (Corresponding author): conceived Sincalide and research ob-jectives, designed and performed experiments, gathered and analyzed data, drafted and critically revised the manuscript, and approved the final version. KKM (Contributor): designed and performed experiments, gathered and analyzed data, drafted part of the article and approved the final version. LG (Contributor): conceived hypothesis and research objectives, designed experiments, analyzed and interpreted data, critically revised the manuscript and approved the final version.
    JR (Contributor): conceived hypothesis and research objectives, critically revised the manuscript and approved the final version.
    MA (Contributor): conceived hypothesis and research objectives, critically revised the manuscript and approved the final version.
    SP (Contributor): conceived hypothesis and research objectives, designed experiments, analyzed and interpreted data, critically revised the manuscript and approved the final version. NT (Contributor): conceived hypothesis and research objectives, designed experiments, analyzed and NT (Contributor): conceived hy-pothesis and research objectives, designed experiments, analyzed and interpreted data, critically revised the manuscript and approved the final version.
    Acknowledgement
    The NorthWest Centre of Advanced Drug Delivery (NoWCADD) established at the University of Manchester in collaboration with AstraZeneca. Dr Enrique Lallana and Dr Julio Rios de La Rosa are gratefully acknowledged for both discussions and experimental help. The Bioimaging Facility of the Faculty of Life Sciences (University of Manchester) is maintained with grants from BBSRC, Wellcome Trust, and the University of Manchester Strategic Fund. The research was funded by Innovate UK project number 101710.
    Appendix A. Supplementary data
    References
    Contents lists available at ScienceDirect
    Cancer Letters
    journal homepage: www.elsevier.com/locate/canlet
    Original Articles
    CD90 highly expressed population harbors a stemness signature and creates T an immunosuppressive niche in pancreatic cancer
    Juanjuan Shia, Ping Lua, Wenyan Shenb, Ruizhe Hec, Min-Wei Yangc, Yuan Fangd, Yong-Wei Sunc,∗∗∗, Ningning Niua,∗∗, Jing Xuea,∗
    a State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Renji Hospital, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China b Department of Clinical Laboratory, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    c Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    d Department of General Surgery & Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    Keywords:
    Pancreatic ductal adenocarcinoma (PDAC)
    Stemness
    Monocyte/macrophage
    Immunosuppressive 
    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 (CD90hi) population in PDAC cells harbors high stemness features and tumor-igenicity. Notably, CD90 acts as an anchor for monocyte/macrophage adhesion, providing a physical interaction between CD90hi cells and monocytes/macrophages. In response, the crosstalk between CD90hi 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 CD90hi 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. r> 1. Introduction
    Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic tumors, is characterized by a highly malignant and poor prognosis, with a five-year survival rate of less than 8% [1–3]. Despite recent advances in diagnosis and surgery, the survival of PDAC patients has changed little in the past two decades. Cancer stem cells (CSCs), defined by their abilities to self-renew, repopulate and undergo in vivo tumorigenicity, are believed to contribute to tumor initiation, relapse and therapeutic resistance [4–6]. Therefore, the identification and mechanistic study of CSCs are urgently needed.