Gamma interferon-mediated superinduction of B7-H1 in PTEN-deficient glioblastoma: a paradoxical mechanism of immune evasion

γ干扰素介导的PTEN缺陷型胶质母细胞瘤中B7-H1的超诱导:一种矛盾的免疫逃逸机制

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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.

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