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- Title
Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma.
- Authors
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.
- Abstract
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.
- Subjects
CANCER immunotherapy; CANCER invasiveness; IMMUNOSUPPRESSIVE agents; GLIOMAS; GLIOBLASTOMA multiforme; TUMOR suppressor proteins; PREVENTION
- Publication
Nature Medicine, 2007, Vol 13, Issue 1, p84
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1517