OVEREXPRESSION OF B7-H4 IN TUMOR INFILTRATED DENDRITIC CELLS
OVEREXPRESSION OF B7-H4 IN TUMOR INFILTRATED DENDRITIC CELLS
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DOI：
10.1080/15321819.2011.578190
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Huang, Jian-An
中科院分区：
文献类型：
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作者：
Cheng, Chen;Qu, Qiu-Xia;Huang, Jian-An
DCs浸润性肿瘤表现为表型和功能缺陷。B7-H4因其在T细胞反应中的抑制作用而被强调。在本研究中，我们发现B7-H4在imDC中适度表达，并被IL-10上调，而在体外，肿瘤坏死因子-α可以拮抗IL-10对DC表达B7-H4的上调作用。此外，肿瘤浸润性DC高水平表达B7-H4。阻断树突状细胞高表达的B7-H4可显著促进T细胞增殖和干扰素-γ的产生。此外，肿瘤组织中存在较高水平的IL-10和肿瘤坏死因子-α，提示肿瘤坏死因子-α不能拮抗IL-10对DC表达B7-H4的影响。提示肿瘤环境可能导致局部DC表型紊乱，B7-H4的高表达可能参与了肿瘤浸润性DC的免疫侵袭。
DCs infiltrated tumors appears to be phenotypically and functionally defective. B7-H4 was highlighted for its inhibitory role in T cell responses. In this study, we showed that B7-H4 was moderately expressed in imDCs, and up-regulated by IL-10, and TNF-alpha could counteract the up-regulatory effects of IL-10 on expression of B7-H4 in DCs in vitro. Furthermore, tumor infiltrated DCs expressed B7-H4 at high levels. Blockade of B7-H4 expressed in DCs highly resulted in enhanced T cell proliferation and IFN-gamma production significantly. Otherwise, the high level of IL-10 and TNF-a was both detected in the tumor, which suggested that TNF-a can not antagonize the effects of IL-10 on expression of B7-H4 in DCs in vivo. These data indicate that tumor environment may condition local DCs to become dysfunctional in the phenotype, and that the high expression of B7-H4 may contribute to the tumor infiltrated DCs to mediate immune invasion.