Induced expression of B7-H4 on the surface of lung cancer cell by the tumor-associated macrophages: A potential mechanism of immune escape
Induced expression of B7-H4 on the surface of lung cancer cell by the tumor-associated macrophages: A potential mechanism of immune escape
复制标题
肿瘤相关巨噬细胞诱导肺癌细胞表面B7-H4表达：免疫逃逸的潜在机制
DOI：
10.1016/j.canlet.2011.11.017
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发表时间：
2012-04-01
期刊：
影响因子：
9.7
通讯作者：
Huang, Jian-An
中科院分区：
文献类型：
--
作者：
Chen, Cheng;Qu, Qiu-Xia;Huang, Jian-An
B7同源物4（B7-H4）是最近鉴定的B7.1/2（CD 80/86）的同源物，已被描述为发挥共刺激和免疫调节功能。我们在体外和体内研究了B7-H4在肺癌中的表达和功能活性。虽然肺癌细胞系在血浆中组成性表达B7-H4 mRNA和蛋白，但从移植肺癌模型分离的原代肿瘤细胞在表面上表达B7-H4。有趣的是，在移植性肺癌模型中，肿瘤细胞膜结合B7-H4的表达随着肿瘤转化时间的延长而增加。暴露于肿瘤相关巨噬细胞强烈诱导肺癌细胞系上的膜结合B7-H4表达。为了阐明肺癌相关的B7-H4表达的功能意义，我们进行了肺癌细胞与同种异体反应性T细胞的共培养实验。肺癌相关的B7-H4被鉴定为T细胞效应的强抑制剂。此外，B7-H4 mAb在体内具有抑制肿瘤生长的能力。因此，B7-H4表达可能显著影响T细胞肿瘤细胞相互作用的结果，并且肺癌细胞上TAM诱导的膜结合B7-H4代表了肺癌细胞逃避免疫识别和破坏的新机制。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
B7-homolog 4 (B7-H4), a recently identified homolog of B7.1/2 (CD80/86), has been described to exert co-stimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H4 in lung cancer in vitro and in vivo. Although a lung cancer cell line constitutively expressed B7-H4 mRNA and protein in plasma, primary tumor cell isolated from the transplanted lung carcinoma model expressed B7-H4 on the surface. Interestingly, in transplanted lung carcinoma model, the expression of membrane-bound B7-H4 in tumor cells was increased as prolonging of tumor transformation. Exposure to tumor-associated macrophages strongly induced membrane-bound B7-H4 expression on the lung cancer cell line. To elucidate the functional significance of lung cancer-related B7-H4 expression, we performed co-culture experiments of lung cancer cell with allo-reactive T cells. Lung cancer-related B7-H4 was identified as a strong inhibitor of T-cell effect. Furthermore, B7-H4 mAb had an ability to inhibit tumor growth in vivo. B7-H4 expression may thus significantly influence the outcome of T-cell tumor cell interactions and TAM induced membrane-bound B7-H4 on the lung cancer cell represents a novel mechanism by which lung cancer cells evade immune recognition and destruction. (C) 2011 Elsevier Ireland Ltd. All rights reserved.