Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma
Author: ["Andrew T Parsa","James S Waldron","Amith Panner","Courtney A Crane","Ian F Parney","Jeffrey J Barry","Kristine E Cachola","Joseph C Murray","Tarik Tihan","Michael C Jensen","Paul S Mischel","David Stokoe","Russell O Pieper"]
Publication: Nature Medicine
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Abstract
Cancer immunoresistance and immune escape1,2,3 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 cancer4,5,6,7,8,9,10. 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.
Cite this article
Parsa, A., Waldron, J., Panner, A. et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 13, 84–88 (2007). https://doi.org/10.1038/nm1517
