It has been shown that tumors have developed numerous ways to escape tumor specific immune responses. These mechanisms will ultimately not only enhance tumor growth, but also impair the effect of immune based therapies in cancer. Myeloid derived suppressor cells represent a recently identified cell population, which has been shown to impair tumor specific immune responses both in mice and human. We have been able to identify a human counterpart of the initially only in mice described MDSC, which is characterized by the expression of CD14 and low/no levels of HLA-DR. 1. In the past year we have been able to demonstrate that while CD14+HLA-DR low/neg cells induce MDSC in vitro, CD14+HLA-DR+ cells actually induce Th17 cells. Interestingly we have also been able to demonstrate an increase in the frequency of Th17 cells in Hepatocellular Carcinoma patients. Our data suggest that Th17 cell suppress T cells responses through a TGF-beta mediated mechanism. 2. We have analyzed different human MDSC subtypes in patients with Hepatocellular Carcinoma and other tumors and compared their frequency and function. We could demonstrate an increase in the frequency of CD14+HLA-DR low/neg MDSC but not of CD133+CD11b+CD15+ MDSC, which demonstrated superior suppressor function in vitro.3. Finally we have been able to characterize human MDSC in more detail and identified a new marker (S100), which is specific for human MDSCs.
