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PI(3) kinase is associated with a mechanism of immunoresistance in breast and prostate cancer

Oncogene volume 28, pages 306–312 (2009)Cite this article

Abstract

Immune escape describes a critical event whereby tumor cells adopt an immunoresistant phenotype to escape adaptive surveillance. We show that expression of a pivotal negative regulator of T-cell function, B7-H1, correlates with PI(3) kinase activation in breast and prostate cancer patients. B7-H1-mediated immunoresistance can be attenuated by inhibitors of the PI(3) kinase pathway, and is dependent on S6K1-mediated translational regulation of B7-H1 protein. Breast and prostate carcinoma cells with activated PI(3) kinase lose the immunoresistant phenotype after treatment with B7-H1 siRNA. Conversely, breast and prostate carcinoma cells with minimal PI(3) kinase activation adopt an immunoresistant phenotype when engineered to overexpress B7-H1 protein. These observations describe a mechanism for immune escape from tumor dormancy in humans that relates to oncogenesis.

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Acknowledgements

We thank Pramod Srivastava and C David James for critical review of the manuscript, as well as the UCSF cancer center for providing tissue with known PI3K activation status. ATP was supported in part by a K08 grant from the National Institute of Neurological Disorder and Stroke, a career development award from Brain Specialized Programs of Research Excellence (SPORE) of the National Cancer Institute, the Seibrandt Vaccine Fund and the Khatib Foundation.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA

    C A Crane, A Panner, J C Murray, S P Wilson, R O Pieper & A T Parsa

  2. Department of Dermatology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    H Xu & L Chen

  3. Department of Pathology and Urology, University of California San Francisco, San Francisco, CA, USA

    J P Simko

  4. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA

    F M Waldman

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  1. C A Crane
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  2. A Panner
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Correspondence to A T Parsa.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Crane, C., Panner, A., Murray, J. et al. PI(3) kinase is associated with a mechanism of immunoresistance in breast and prostate cancer. Oncogene 28, 306–312 (2009). https://doi.org/10.1038/onc.2008.384

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