Source:http://linkedlifedata.com/resource/pubmed/id/20822910
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2010-11-1
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| pubmed:abstractText |
The ability of glioma cells to escape the immune system remains a significant barrier to successful immunotherapy. Here we demonstrate that loss of the PTEN tumor suppressor gene, with associated activation of the PI3K/Akt/mTOR pathway, leads to a human glioma phenotype that induces autologous T-cell apoptosis upon contact. The PTEN status of pathologically confirmed glioblastoma specimens was defined, and primary cultures established after surgical resection of tumor from 26 patients. Autologous T-cells were isolated from these patients, and after T-cell activation was induced, these cells were co-cultured with matched autologous glioma cells, either alone, or after treatment with one of three inhibitors of the PI3K/Akt/mTOR pathway. When co-cultured with autologous T-cells, PTEN wild-type tumor cells induced apoptosis in a minimal number of activated T-cells (6-12% of T-cells), whereas tumors with PTEN loss induced much more profound levels of T-cell apoptosis (42-56% of T-cells). Prior treatment of PTEN-deficient tumor cells with specific inhibitors of the PI3K/Akt/mTOR pathway diminished T-cell apoptosis to levels seen after co-culture with wild-type PTEN tumor cells, suggesting that PTEN loss confers this immunoresistant phenotype through the PI3K/Akt/mTOR pathway. These results suggest that PTEN-deficient glioblastoma patients are suboptimal candidates for immunotherapy. In addition, our results raise the possibility of combining T-cell based immunotherapy protocols with clinical inhibitors of the PI3K/Akt/mTOR pathway.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
|
| pubmed:issn |
1532-2653
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
17
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1543-7
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| pubmed:meshHeading |
pubmed-meshheading:20822910-Apoptosis,
pubmed-meshheading:20822910-Brain Neoplasms,
pubmed-meshheading:20822910-Cell Separation,
pubmed-meshheading:20822910-Cells, Cultured,
pubmed-meshheading:20822910-Coculture Techniques,
pubmed-meshheading:20822910-Flow Cytometry,
pubmed-meshheading:20822910-Genes, Tumor Suppressor,
pubmed-meshheading:20822910-Glioblastoma,
pubmed-meshheading:20822910-Humans,
pubmed-meshheading:20822910-Immunohistochemistry,
pubmed-meshheading:20822910-Immunotherapy,
pubmed-meshheading:20822910-Lymphocyte Activation,
pubmed-meshheading:20822910-PTEN Phosphohydrolase,
pubmed-meshheading:20822910-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:20822910-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20822910-Signal Transduction,
pubmed-meshheading:20822910-T-Lymphocytes,
pubmed-meshheading:20822910-TOR Serine-Threonine Kinases
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| pubmed:year |
2010
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| pubmed:articleTitle |
Implications for immunotherapy of tumor-mediated T-cell apoptosis associated with loss of the tumor suppressor PTEN in glioblastoma.
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| pubmed:affiliation |
Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94123, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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