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

AT Parsa, JS Waldron, A Panner, CA Crane… - Nature medicine, 2007 - nature.com
AT Parsa, JS Waldron, A Panner, CA Crane, IF Parney, JJ Barry, KE Cachola, JC Murray
Nature medicine, 2007nature.com
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 …
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.
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