B7-H1 expression is regulated by MEK/ERK signaling pathway in anaplastic large cell lymphoma and Hodgkin lymphoma
B7-H1 expression is regulated by MEK/ERK signaling pathway in anaplastic large cell lymphoma and Hodgkin lymphoma
复制标题
DOI：
10.1111/j.1349-7006.2009.01302.x
复制
发表时间：
2009-11-01
期刊：
影响因子：
5.7
通讯作者：
Uchiyama, Takashi
中科院分区：
文献类型：
--
作者：
Yamamoto, Ryo;Nishikori, Momoko;Uchiyama, Takashi
B7-H1是B7家族的成员，通过其受体程序性死亡-1（PD-1）抑制T细胞的功能。我们检测了间变性大细胞淋巴瘤（ALCL）和霍奇金淋巴瘤（HL）中B7-H1的表达，发现它在临床样本和细胞系中均组成性表达。在间变性淋巴瘤激酶阳性（ALK+）ALCL细胞中，通过阻断细胞外信号调节激酶（ERK）信号传导抑制B7-H1表达，并通过佛波醇13-肉豆蔻酸酯12-乙酸酯刺激增强ERK活性上调B7-H1表达，表明ALCL中B7-H1表达受ERK信号通路调节。ERK是ALK+ALCL中核磷蛋白（NPM）/ALK信号传导的下游介质之一，药理学抑制ALK可使ERK去磷酸化并下调B7-H1。通过将构建体引入人非ALCL淋巴细胞系中（导致B7-H1表达），也证明了NPM/ALK参与B7-H1表达。在HL的情况下，B7-H1的表达被证明是依赖于ERK和p38丝裂原活化蛋白激酶（MAPK）信号通路。这些结果表明，B7-H1的表达是由共同的ERK信号通路在ALCL和HL细胞控制。我们的研究结果为这些表达B7-H1的肿瘤提供了一种潜在有效的免疫策略。（Cancer Sci 2009）。
B7-H1 is a member of the B7 family that inhibits the function of T-cells through its receptor programmed death-1 (PD-1). We examined B7-H1 expression in anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) and found that it was constitutively expressed in both clinical samples and cell lines. In anaplastic lymphoma kinase-positive (ALK+) ALCL cells, B7-H1 expression was suppressed by the blocking of extracellular signal-regulated kinase (ERK) signaling and upregulated by the augmentation of ERK activity by phorbol 13-myristate 12-acetate stimulation, suggesting that B7-H1 expression is regulated by ERK signaling pathway in ALCL. ERK is one of the downstream mediators of nucleophosmin (NPM)/ALK signaling in ALK+ALCL, and pharmacological inhibition of ALK was shown to dephosphorylate ERK and down-regulate B7-H1. The involvement of NPM/ALK in B7-H1 expression was also demonstrated by introducing the construct into human non-ALCL lymphoid cell lines, which resulted in B7-H1 expression. In the case of HL, B7-H1 expression was shown to be dependent on the ERK and p38 mitogen-activated protein kinase (MAPK) signaling pathways. These results suggest that B7-H1 expression is controlled by common ERK signaling pathways in ALCL and HL cells. Our findings provide a potentially effective immunotherapeutic strategy for these B7-H1-expressing tumors. (Cancer Sci 2009).