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CD73: an emerging checkpoint for cancer immunotherapy

    Siqi Chen

    Robert H Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

    ,
    Derek A Wainwright

    Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

    ,
    Jennifer D Wu

    Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

    ,
    Yong Wan

    Department of Obstetrics & Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

    ,
    Daniela E Matei

    Department of Obstetrics & Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

    ,
    Yi Zhang

    Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    &
    Bin Zhang

    *Author for correspondence: Tel.: +1 312 503 2435; Fax: +1 312 503 0189;

    E-mail Address: bin.zhang@northwestern.edu

    Robert H Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

    Published Online:https://doi.org/10.2217/imt-2018-0200

    CD73 is a novel immune checkpoint associated with adenosine metabolism that promotes tumor progression by suppressing antitumor immune response and promoting angiogenesis. The inhibition of CD73, in combination with immune checkpoint blockade, targeted therapy or conventional therapy, improves antitumor effects in numerous preclinical mouse models of cancer. Emerging evidence suggests that the combination of anti-CD73 and immune checkpoint blockade has promising clinical activity in patients with advanced solid tumors. In this review, we will discuss the specific role of CD73 on both tumor cells and nontumor cells in regulating tumor immunity and tumorigenesis and provide an update on the current view of the antitumor activity of targeting CD73 by mAb or small molecule selective inhibitors in preclinical and clinical settings.

    Papers of special note have been highlighted as: • of interest

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