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

C. A. Crane, A. Panner, J. C. Murray, S. P. Wilson, H. Xu, L. Chen, J. P. Simko, F. M. Waldman, R. O. Pieper, A. T. Parsa

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)306-312
Number of pages7
JournalOncogene
Volume28
Issue number2
DOIs
StatePublished - Jan 15 2009

Keywords

  • B7-H1
  • Breast cancer
  • Immunoresistance
  • PI(3) kinase
  • Prostate cancer
  • T cell

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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