Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of the head and neck
Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of the head and neck
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DOI：
10.1111/j.1349-7006.2012.02248.x
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发表时间：
2012-06-01
期刊：
影响因子：
5.7
通讯作者：
Masuyama, Keisuke
中科院分区：
文献类型：
--
作者：
Chikamatsu, Kazuaki;Sakakura, Koichi;Masuyama, Keisuke
骨髓源性抑制细胞（MDSC）代表了一个异质性群体，并有可能通过不同的机制抑制免疫反应。在最近的研究中，一个新的MDSC的子集被确定为标志物CD 14+和HLA-DR-在外周血中的癌症患者。在这项研究中，我们调查了CD 14 + HLA-DR-细胞在头颈部鳞状细胞癌（SCCHN）患者中的比例和特征。正如预期的那样，CD 14 + HLA-DR-细胞的百分比在患者中相对于健康供体显著升高，并且分选的CD 14 + HLA-DR-细胞能够有效地抑制增殖和IFN-？抗CD 3/抗CD 28刺激的T细胞的产生，表明SCCHN患者中的CD 14 + HLA-DR-细胞有助于免疫抑制状态。此外，CD 14 + HLA-DR-细胞显示出比CD 14 + HLA-DR+细胞更高水平的CD 86和PD-L1表达以及转化生长因子（TGF）-β产生。添加抗CD 86 mAb，抗PD-L1 mAb和抗TGF-β mAb部分恢复T细胞增殖和IFN-？结果表明，CD 14 + HLA-DR-细胞的抑制作用似乎是由各种分子介导的，包括共抑制分子和细胞因子。我们的数据表明，CD 14 + HLA-DR-细胞作为有效的免疫抑制细胞，特别是有助于肿瘤从SCCHN患者的宿主免疫系统逃逸。（Cancer Sci 2012; 103：976983）
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)