Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of the head and neck

Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population and have the potential to suppress immune responses via diverse mechanisms. In recent studies, a new subset of MDSC was identified by the markers CD14+ and HLA-DR- in the peripheral blood from cancer patients. In this study, we investigated the proportions and characteristics of CD14+ HLA-DR- cells in patients with squamous cell carcinoma of the head and neck (SCCHN). As expected, the percentage of CD14+ HLA-DR- cells was significantly elevated in patients relative to healthy donors and the sorted CD14+ HLA-DR- cells were able to suppress effectively both the proliferation and IFN-? production of anti-CD3/anti-CD28 stimulated T cells, suggesting that CD14+ HLA-DR- cells in patients with SCCHN contribute to the immune suppressive status. Furthermore, CD14+ HLA-DR- cells revealed a higher level of CD86 and PD-L1 expression and transforming growth factor (TGF)-beta production than CD14+ HLA-DR+ cells. Addition of anti-CD86 mAb, anti-PD-L1 mAb and anti-TGF-beta mAb partially restored T-cell proliferation and IFN-? production, respectively, indicating that the suppressive effects of CD14+ HLA-DR- cells appear to be mediated by various molecules, including coinhibitory molecules and cytokines. Our data suggest that CD14+ HLA-DR- cells act as potent immunosuppressive cells and particularly contribute to tumor escape from the host immune system in patients with SCCHN. (Cancer Sci 2012; 103: 976983)