Abstract
B7 homolog 1 (B7-H1) is a recently discovered immunoresistance protein that is regulated posttranscriptionally after PTEN loss in malignant glioma, a deadly form of brain tumor. Here, the impact of gamma-interferon-mediated activation of B7-H1 was investigated in glioblastoma patients with PTEN loss. Lymphocytes and T cells were selected for apoptosis assays after 1 : 1 coculture with autologous glioma cells. Gamma interferon treatment of PTEN-deficient tumors resulted in superinduction of B7-H1 protein that correlated with increased T-cell apoptosis, an effect dependent upon activation of the PI3-kinase pathway. The combination of PTEN loss and gamma-interferon exposure in glioblastoma patients results in an exceptionally immunoresistant phenotype that may negate adaptive immunity through induction of T-cell apoptosis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / metabolism*
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Antineoplastic Agents / therapeutic use*
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Apoptosis / drug effects
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Apoptosis / physiology
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B7-H1 Antigen
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Brain Neoplasms / drug therapy*
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Brain Neoplasms / immunology
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Brain Neoplasms / physiopathology
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Cell Line, Tumor
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Cells, Cultured
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Coculture Techniques
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Enzyme Inhibitors / pharmacology
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Glioblastoma / drug therapy*
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Glioblastoma / immunology
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Glioblastoma / physiopathology
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Humans
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Interferon-gamma / therapeutic use*
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Lymphocytes / drug effects
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Lymphocytes / physiology
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PTEN Phosphohydrolase / deficiency*
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PTEN Phosphohydrolase / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Signal Transduction / drug effects
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T-Lymphocytes / drug effects
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T-Lymphocytes / physiology
Substances
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Antigens, CD
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Antineoplastic Agents
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B7-H1 Antigen
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CD274 protein, human
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Enzyme Inhibitors
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Phosphoinositide-3 Kinase Inhibitors
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Interferon-gamma
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PTEN Phosphohydrolase
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PTEN protein, human