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

B7-H1 is a recently discovered immunoresistance protein that is regulated post-transcriptionally 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 co-culture 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 PI3Kinase 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.