Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
Cancer Sci. 2012 Jun;103(6):976-83. doi: 10.1111/j.1349-7006.2012.02248.x. Epub 2012 Apr 11.
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.
髓系来源的抑制细胞（MDSC）是一个异质性群体，具有通过多种机制抑制免疫反应的潜力。在最近的研究中，通过癌症患者外周血中的标志物 CD14(+)和 HLA-DR(-)，鉴定出了一种新的 MDSC 亚群。在这项研究中，我们研究了头颈部鳞状细胞癌（SCCHN）患者中 CD14(+) HLA-DR(-)细胞的比例和特征。正如预期的那样，与健康供体相比，CD14(+) HLA-DR(-)细胞的比例在患者中显著升高，并且分选的 CD14(+) HLA-DR(-)细胞能够有效抑制抗-CD3/抗-CD28 刺激的 T 细胞的增殖和 IFN-γ产生，这表明 SCCHN 患者中的 CD14(+) HLA-DR(-)细胞有助于免疫抑制状态。此外，CD14(+) HLA-DR(-)细胞显示出比 CD14(+) HLA-DR(+)细胞更高水平的 CD86 和 PD-L1 表达和转化生长因子（TGF）-β产生。添加抗 CD86 mAb、抗 PD-L1 mAb 和抗 TGF-β mAb 分别部分恢复了 T 细胞的增殖和 IFN-γ产生，表明 CD14(+) HLA-DR(-)细胞的抑制作用似乎是由多种分子介导的，包括共抑制分子和细胞因子。我们的数据表明，CD14(+) HLA-DR(-)细胞作为有效的免疫抑制细胞，特别是在 SCCHN 患者中，有助于肿瘤逃避宿主免疫系统的攻击。
