Myeloid derived suppressor cells inhibit natural killer... : Hepatology (original) (raw)

Hepatobiliary Malignancies

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

Hoechst, Bastian1,2†; Voigtlaender, Torsten1,2†; Ormandy, Lars1¶; Gamrekelashvili, Jaba1,2; Zhao, Fei1,2; Wedemeyer, Heiner1; Lehner, Frank3; Manns, Michael P.1; Greten, Tim F.1,2*‡ п; Korangy, Firouzeh1,2*‡

1 Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany

2 Twincore Center for Experimental and Clinical Infection Research, Hannover, Germany

3 Departments of Visceral and Transplantation Surgery, Medical School, Medical School Hannover, Hannover, Germany

¶ Department of Forensic Medicine, University of Göttingen, Germany

* Department of Gastroenterology, Hepatology and Endocrinology, Twincore Center for Experimental and Clinical Research, Medical School Hannover, Carl Neuberg Straße 1, 30625 Hannover, Germany

Email:[email protected]

Received January 10, 2009; accepted April 21, 2009.

Published online 23 June 2009 in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: Deutsche Forschungsgemeinschaft (DFG); Grant Number: KFO119; Grant sponsor: H.W. & J. Hector Foundation; Grant sponsor: Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Immunotherapy of Cancer.

# Potential conflict of interest: Nothing to report.

† These authors contributed equally to this work.

‡ These authors are equal senior authors.

п fax: 49-511-22 00 27 203.

Additional Supporting Information may be found in the online version of this article.

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.)