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.
Yamamoto
Ryo
R
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Nishikori
Momoko
M
Tashima
Masaharu
M
Sakai
Tomomi
T
Ichinohe
Tatsuo
T
Takaori-Kondo
Akifumi
A
Ohmori
Katsuyuki
K
Uchiyama
Takashi
T
D015703:Antigens, CD / Q000032:analysis* / Q000502:physiology; D060890:B7-H1 Antigen; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000502:physiology
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases
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