Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma

Cancer immunoresistance and immune escape may play important roles in tumor progression and pose obstacles for immunotherapy. Expression of the immunosuppressive protein B7 homolog 1 (B7-H1), also known as programmed death ligand-1 (PD-L1), is increased in many pathological conditions, including can...

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Veröffentlicht in:Nature medicine 2007-01, Vol.13 (1), p.84-88
Hauptverfasser: Parsa, Andrew T, Waldron, James S, Panner, Amith, Crane, Courtney A, Parney, Ian F, Barry, Jeffrey J, Cachola, Kristine E, Murray, Joseph C, Tihan, Tarik, Jensen, Michael C, Mischel, Paul S, Stokoe, David, Pieper, Russell O
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Sprache:eng
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Zusammenfassung:Cancer immunoresistance and immune escape may play important roles in tumor progression and pose obstacles for immunotherapy. Expression of the immunosuppressive protein B7 homolog 1 (B7-H1), also known as programmed death ligand-1 (PD-L1), is increased in many pathological conditions, including cancer. Here we show that expression of the gene encoding B7-H1 increases post transcriptionally in human glioma after loss of phosphatase and tensin homolog (PTEN) and activation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway. Tumor specimens from individuals with glioblastoma multiforme (GBM) had levels of B7-H1 protein that correlated with PTEN loss, and tumor-specific T cells lysed human glioma targets expressing wild-type PTEN more effectively than those expressing mutant PTEN. These data identify a previously unrecognized mechanism linking loss of the tumor suppressor PTEN with immunoresistance, mediated in part by B7-H1.
ISSN:1078-8956
1546-170X
DOI:10.1038/nm1517