Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor

Authors

  • Bastian Hoechst,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
    2. Twincore Center for Experimental and Clinical Infection Research, Hannover, Germany
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    • These authors contributed equally to this work.

  • Torsten Voigtlaender,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
    2. Twincore Center for Experimental and Clinical Infection Research, Hannover, Germany
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    • These authors contributed equally to this work.

  • Lars Ormandy,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
    Current affiliation:
    1. Department of Forensic Medicine, University of Göttingen, Germany
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  • Jaba Gamrekelashvili,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
    2. Twincore Center for Experimental and Clinical Infection Research, Hannover, Germany
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  • Fei Zhao,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
    2. Twincore Center for Experimental and Clinical Infection Research, Hannover, Germany
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  • Heiner Wedemeyer,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
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  • Frank Lehner,

    1. Departments of Visceral and Transplantation Surgery, Medical School, Medical School Hannover, Hannover, Germany
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  • Michael P. Manns,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
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  • Tim F. Greten,

    Corresponding author
    1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
    2. Twincore Center for Experimental and Clinical Infection Research, Hannover, Germany
    • Department of Gastroenterology, Hepatology and Endocrinology, Twincore Center for Experimental and Clinical Research, Medical School Hannover, Carl Neuberg Straße 1, 30625 Hannover, Germany
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    • These authors are equal senior authors.

    • fax: 49-511-22 00 27 203.

  • Firouzeh Korangy

    Corresponding author
    1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
    2. Twincore Center for Experimental and Clinical Infection Research, Hannover, Germany
    • Department of Gastroenterology, Hepatology and Endocrinology, Twincore Center for Experimental and Clinical Research, Medical School Hannover, Carl Neuberg Straße 1, 30625 Hannover, Germany
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    • These authors are equal senior authors.


  • Potential conflict of interest: Nothing to report.

Abstract

Several immune suppressive mechanisms that evade the host immune response have been described in patients with hepatocellular carcinoma (HCC); one of these mechanisms is expansion of myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to inhibit T cell responses in tumor-bearing mice, but little is known about these cells in humans. Here, we have analyzed and characterized the effect of MDSCs on the innate immune system, in particular, their interaction with natural killer (NK) cells in patients with HCC. MDSCs from patients with HCC inhibited autologous NK cell cytotoxicity and cytokine secretion when cultured together in vitro. This suppression was dependent on cell contact, but did not rely on the arginase activity of MDSCs, which is a hallmark function of these cells. However, MDSC-mediated inhibition of NK cell function was dependent mainly on the NKp30 on NK cells. Conclusion: Our study suggests a new role for MDSCs in patients with HCC in disarming the innate immune system and further contributing to the immune suppressor network in these patients. These findings have important implications when designing immunotherapy protocols. (HEPATOLOGY 2009.)

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