Journal Article

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

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

2009

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Adenocarcinoma - enzymology / Adenocarcinoma - immunology / Adenocarcinoma - pathology / Antigens, CD - genetics / Antigens, CD - physiology / Apoptosis / B7-H1 Antigen / Biological and medical sciences / Breast cancer / Breast Neoplasms - enzymology / Breast Neoplasms - immunology / Breast Neoplasms - pathology / Care and treatment / Cell Biology / Cell Line, Tumor - drug effects / Cell Line, Tumor - enzymology / Cell Line, Tumor - immunology / Cell physiology / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Female / Fundamental and applied biological sciences. Psychology / Gene Expression Regulation, Neoplastic / Gene Knockdown Techniques / Genetic aspects / Genotype & phenotype / Gynecology. Andrology. Obstetrics / Health aspects / Human Genetics / Humans / Immune response / Immune system / Internal Medicine / Kinases / Leukocytes / Male / Mammary gland diseases / Medical sciences / Medicine / Medicine & Public Health / Molecular and cellular biology / Neoplasm Proteins - antagonists & inhibitors / Neoplasm Proteins - genetics / Neoplasm Proteins - physiology / Nephrology. Urinary tract diseases / Oncology / Phenotype / Phosphatidylinositol 3-Kinases - antagonists & inhibitors / Phosphatidylinositol 3-Kinases - physiology / Prostate cancer / Prostatic Neoplasms - enzymology / Prostatic Neoplasms - immunology / Prostatic Neoplasms - pathology / Protein Kinase Inhibitors - pharmacology / Protein kinases / PTEN Phosphohydrolase - physiology / Recombinant Fusion Proteins - physiology / Ribosomal Protein S6 Kinases - physiology / RNA, Small Interfering - pharmacology / short-communication / T-Lymphocytes, Cytotoxic - immunology / Tumor Escape - drug effects / Tumor Escape - genetics / Tumor Escape - immunology / Tumors / Tumors of the urinary system / Urinary tract. Prostate gland