Respiratory Department, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
Cancer Lett. 2012 Apr 1;317(1):99-105. doi: 10.1016/j.canlet.2011.11.017. Epub 2011 Nov 20.
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.
B7 同源物 4（B7-H4）是 B7.1/2（CD80/86）的新同系物，已被描述为具有共刺激和免疫调节功能。我们在体外和体内研究了肺癌中 B7-H4 的表达和功能活性。虽然肺癌细胞系在血浆中持续表达 B7-H4 的 mRNA 和蛋白，但从移植的肺癌模型中分离出的原代肿瘤细胞在表面表达 B7-H4。有趣的是，在移植的肺癌模型中，随着肿瘤转化时间的延长，肿瘤细胞表面结合的 B7-H4 表达增加。肿瘤相关巨噬细胞的暴露强烈诱导肺癌细胞系表面结合的 B7-H4 表达。为了阐明与肺癌相关的 B7-H4 表达的功能意义，我们进行了肺癌细胞与同种反应性 T 细胞的共培养实验。研究表明，与肺癌相关的 B7-H4 是 T 细胞效应的强抑制剂。此外，B7-H4 mAb 具有抑制体内肿瘤生长的能力。因此，B7-H4 的表达可能会显著影响 T 细胞与肿瘤细胞相互作用的结果，而 TAM 诱导的肺癌细胞表面结合的 B7-H4 代表了肺癌细胞逃避免疫识别和破坏的新机制。
