Gamma interferon-mediated superinduction of B7-H1 in PTEN-deficient glioblastoma: a paradoxical mechanism of immune evasion.
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.
Han
Seunggu J
SJ
Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94117, USA.
Ahn
Brian J
BJ
Waldron
James S
JS
Yang
Isaac
I
Fang
Shanna
S
Crane
Courtney A
CA
Pieper
Russell O
RO
Parsa
Andrew T
AT
D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D060890:B7-H1 Antigen; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology
D015703:Antigens, CD; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D004791:Enzyme Inhibitors; D007371:Interferon-gamma; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C423236:CD274 protein, human; C494929:PTEN protein, human