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


CONCLUSIONS
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.
Hoechst
Bastian
B
Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany.
Voigtlaender
Torsten
T
Ormandy
Lars
L
Gamrekelashvili
Jaba
J
Zhao
Fei
F
Wedemeyer
Heiner
H
Lehner
Frank
F
Manns
Michael P
MP
Greten
Tim F
TF
Korangy
Firouzeh
F
D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology*; D008297:Male; D022423:Myeloid Cells / Q000276:immunology*; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000502:physiology*
D055628:Natural Cytotoxicity Triggering Receptor 3