PI(3) Kinase Is Associated With a Mechanism of Immunoresistance in Breast and Prostate Cancer

Oncogene. 2009 Jan 15;28(2):306-12. doi: 10.1038/onc.2008.384. Epub 2008 Oct 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • B7-H1 Antigen
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / enzymology
  • Cell Line, Tumor / immunology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • PTEN Phosphohydrolase / physiology
  • Phenotype
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphoinositide-3 Kinase Inhibitors
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Small Interfering / pharmacology
  • Recombinant Fusion Proteins / physiology
  • Ribosomal Protein S6 Kinases / physiology
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Escape / drug effects
  • Tumor Escape / genetics
  • Tumor Escape / immunology*

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • Neoplasm Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Ribosomal Protein S6 Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human