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Rationally combining anti-VEGF therapy with checkpoint inhibitors in hepatocellular carcinoma

    Tai Hato

    Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

    Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan

    ,
    Andrew X Zhu

    Hematology/Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA

    &
    Dan G Duda

    *Author for correspondence:

    E-mail Address: gduda@partners.org

    Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

    Published Online:https://doi.org/10.2217/imt.15.126

    Hepatocellular carcinoma (HCC) is a fatal disease with rising incidence in the world. For advanced HCC, sorafenib, a multikinase inhibitor, is the only systemic therapy with proven survival benefits. Sorafenib is a pan-VEGF receptor inhibitor, and thus many studies have focused its antivascular effects. But VEGF also acts as an immunosuppressive molecule. VEGF can inhibit maturation of dendritic cells, promote immune suppressive cell infiltration and enhance immune checkpoint molecules expression. On the other hand, potent VEGF inhibition may increase tumor hypoxia, which could hinder antitumor immunity or immunotherapy. Thus, achieving synergy when combining anti-VEGF therapy with immunotherapy may require proper polarization of the tumor microenvironment by dose titration or combination with other immunomodulating agents.

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

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