髓源性抑制细胞通过B7-H1促进肺癌生长的年龄相关性增加。
Myeloid-derived suppressor cells promote age-related increase of lung cancer growth via B7-H1.
作者信息
Chen Siwen, Liu Hongmei, Su Nan, Zhang Guangbo, Wang Ling
机构信息
Special Procurement Ward, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
Respiratory Intensive Care Unit, Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
出版信息
Exp Gerontol. 2015 Jan;61:84-91. doi: 10.1016/j.exger.2014.12.001. Epub 2014 Dec 2.
Accumulation of myeloid-derived suppressor cells (MDSCs) in aged hosts contribute to the age-related increase of susceptibility to murine breast adenocarcinoma and co-stimulatory molecules expressed in MDSCs are essential for MDSCs-mediated immune suppression. However, the co-stimulatory molecules that exert a direct effect on MDSCs-mediated age-dependent tumor susceptibility and the regulatory mechanism of their expression remain unclear. In the present study, we found that accumulation of MDSCs in aged mice was closely correlated with age-dependent enhanced growth of lung cancer. Further analysis revealed that B7-H1 was highly expressed in the MDSCs of 18-month but not in 2-month old mice. Accordingly, inhibition of B7-H1 with B7-H1 specific antibody significantly reactivated T cells and reduced the tumor progression mediated by MDSCs. In addition, IL-10 released from 18-month old mice stimulated the expression of B7-H1 on MDSCs. These results suggest that B7-H1 expressed on MDSCs is a novel target for reducing lung cancer susceptibility as the age increases.
髓源性抑制细胞（MDSCs）在老年宿主中的积累导致了与年龄相关的小鼠乳腺腺癌易感性增加，且MDSCs中表达的共刺激分子对于MDSCs介导的免疫抑制至关重要。然而，对MDSCs介导的年龄依赖性肿瘤易感性产生直接影响的共刺激分子及其表达的调控机制仍不清楚。在本研究中，我们发现老年小鼠中MDSCs的积累与年龄依赖性的肺癌生长增强密切相关。进一步分析显示，B7-H1在18月龄小鼠的MDSCs中高表达，而在2月龄小鼠中不表达。因此，用B7-H1特异性抗体抑制B7-H1可显著重新激活T细胞，并减少MDSCs介导的肿瘤进展。此外，18月龄小鼠释放的IL-10刺激了MDSCs上B7-H1的表达。这些结果表明，MDSCs上表达的B7-H1是随着年龄增长降低肺癌易感性的一个新靶点。
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