Grizzle William E, Xu Xin, Zhang Shuangqin, Stockard Cecil R, Liu Cunren, Yu Shaohua, Wang Jianhua, Mountz John D, Zhang Huang-Ge
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
Mech Ageing Dev. 2007 Nov-Dec;128(11-12):672-80. doi: 10.1016/j.mad.2007.10.003. Epub 2007 Oct 22.
In this study, our data show that in young BXD12 mice, the implanted TS/A tumor regressed in 4 weeks after implantation, and this regression was associated with extensive T cell infiltration. In contrast, in old BXD12 mice, it was observed that there was rapid tumor growth by 7 weeks. T cell cytotoxicity against TS/A tumor cells exhibited a significant age-related decline, which was correlated with a decline in CD3(+) T cell infiltration of the tumor. Furthermore, the decline of T cell tumor cytotoxicity in aged BXD12 mice was also correlated with the accumulation of CD11b(+)Gr1(+) myeloid-derived suppressor cells in the spleen. Adoptive transfer of these accumulated CD11b(+)Gr1(+)cells from aged mice to 2-month-old BXD12 mice led to the delay of the rejection of implanted tumor cells. The depletion of CD11b(+)Gr1(+)cells from aged BXD12 mice led to the slower growth of tumor. Induction of arginase 1 in myeloid cells isolated from aged mice plays a partial role in immune suppression of T cell cytotoxicity. Thus, the accumulation of immunosuppresssing myeloid cells appears to contribute to the increase of tumor susceptibility as the age of mice increases.
在本研究中，我们的数据表明，在年轻的BXD12小鼠中，植入的TS/A肿瘤在植入后4周内消退，且这种消退与广泛的T细胞浸润有关。相比之下，在年老的BXD12小鼠中，观察到肿瘤在7周时快速生长。T细胞对TS/A肿瘤细胞的细胞毒性表现出显著的年龄相关性下降，这与肿瘤中CD3(+) T细胞浸润的减少相关。此外，年老的BXD12小鼠中T细胞肿瘤细胞毒性的下降也与脾脏中CD11b(+)Gr1(+)髓源性抑制细胞的积累相关。将这些来自年老小鼠的积累的CD11b(+)Gr1(+)细胞过继转移到2月龄的BXD12小鼠中导致植入肿瘤细胞排斥反应的延迟。从年老的BXD12小鼠中去除CD11b(+)Gr1(+)细胞导致肿瘤生长减慢。从年老小鼠分离的髓细胞中精氨酸酶1的诱导在T细胞细胞毒性的免疫抑制中起部分作用。因此，随着小鼠年龄的增加，免疫抑制性髓细胞的积累似乎导致肿瘤易感性增加。
