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Cancer Sci. 2012 Jun;103(6):976-83. doi: 10.1111/j.1349-7006.2012.02248.x. Epub 2012 Apr 11.

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

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1
Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan. tikamatu@gunma-u.ac.jp

Abstract

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-γ 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)-β production than CD14(+) HLA-DR(+) cells. Addition of anti-CD86 mAb, anti-PD-L1 mAb and anti-TGF-β mAb partially restored T-cell proliferation and IFN-γ 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.

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