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

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

Research output: Contribution to journalArticle

840 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)84-88
Number of pages5
JournalNature Medicine
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Parsa, A. T., Waldron, J. S., Panner, A., Crane, C. A., Parney, I. F., Barry, J. J., Cachola, K. E., Murray, J. C., Tihan, T., Jensen, M. C., Mischel, P. S., Stokoe, D., & Pieper, R. O. (2007). Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nature Medicine, 13(1), 84-88. https://doi.org/10.1038/nm1517