B7-H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer
B7-H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer
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DOI：
10.1016/j.clim.2008.07.030
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发表时间：
2008-12-01
影响因子：
8.6
通讯作者：
Yang, Rongcun
中科院分区：
文献类型：
--
作者：
Liu, Yu;Zeng, Bin;Yang, Rongcun
骨髓源性抑制细胞（MDSC）在荷瘤宿主中积累，并与免疫抑制有关。在此，我们描述了从携带1D 8卵巢癌的小鼠的腹水和脾中获得的Gr-1（+）CD 11b（+）MDSC的B7-H1（CD 274）、PD-1（CD 279）和CTLA 4（CD 152）的高水平表达，而B7-DC（CD 273）、CD 40和CD 86不存在。相比之下，在来自幼稚小鼠的Gr-1（+）CD 11b（+）细胞上未检测到B7-H1、PD-1和CTLA-4表达。1D 8卵巢癌细胞可诱导幼稚小鼠Gr-1（+）CD 11b（+）细胞表达B7-H1。来自1D 8荷瘤小鼠的Gr-1（+）CD 11b（+）细胞显著抑制抗原特异性免疫应答，而来自未处理小鼠的Gr-1（+）CD 11b（+）细胞则没有。siRNA介导的1D 8荷瘤小鼠Gr-1（+）CD 11b（+）细胞中B7-H1的敲低减轻了抗原特异性免疫应答的抑制。通过B7-H1对Gr-1（+）CD 11b（+）骨髓细胞的抗原特异性免疫应答的抑制由CD 4（+）CD 25（+）Foxp 3（+）T调节细胞介导，需要PD-1。B7-H1或PD-1的抗体阻断延缓了小鼠1D 8肿瘤的生长。这表明由卵巢癌1D 8小鼠模型触发的Gr-1（+）CD 11b（+）骨髓细胞上的B7-H1表达通过与CD 4（+）CD 25（+）Foxp 3（+）调节性T细胞上的PD-1相互作用抑制抗原特异性免疫。(C)2008年爱思唯尔公司All rights reserved.
Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and are associated with immune suppression. Here, we described high level of expression of B7-H1 (CD274), PD-1 (CD279) and CTLA4 (CD152) by Gr-1(+)CD11b(+) MDSCs obtained from both ascites and spleens of mice bearing the 1D8 ovarian carcinoma, whereas B7-DC (CD273), CD40 and CD86 were absent. In contrast, B7-H1, PD-1 and CTLA-4 expression was not detected on Gr-1(+)CD11b(+) cells from naive mice. Expression of B7-H1 by Gr-1(+)CD11b(+) cells from naive mice could be induced by co-culture with 1D8 ovarian carcinoma cells. Gr-1(+)CD11b(+) cells derived from 1D8 tumor-bearing mice markedly suppressed antigen-specific immune responses, whereas Gr-1(+)CD11b(+) cells from naive mice did not. siRNA-mediated knockdown of B7-H1 in Gr-1(+)CD11b(+) cells of 1D8 tumor-bearing mice alleviated suppression of antigen-specific immune responses. Suppression of antigen-specific immune responses via B7-H1 on Gr-1(+)CD11b(+) myeloid cells was mediated by CD4(+)CD25(+) Foxp3(+) T regulatory cells and required PD-1. Antibody blockade of either B7-H1 or PD-1 retarded the growth of 1D8 tumor in mice. This suggests that expression of B7-H1 on Gr-1(+)CD11b(+) myeloid cells triggered by the 1D8 mouse model of ovarian carcinoma suppresses antigen-specific immunity via interaction with PD-1 on CD4(+)CD25(+) Foxp3(+) regulatory T cells. (C) 2008 Elsevier Inc. All rights reserved.