B7‐H1 expression is regulated by MEK/ERK signaling pathway in anaplastic large cell lymphoma and Hodgkin lymphoma

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)