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

doi:10.1038/onc.2008.384

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 journal › Article › peer-review

113 Scopus citations

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 language	English (US)
Pages (from-to)	306-312
Number of pages	7
Journal	Oncogene
Volume	28
Issue number	2
DOIs	https://doi.org/10.1038/onc.2008.384
State	Published - Jan 15 2009
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Genetics
Molecular Biology
Cancer Research

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10.1038/onc.2008.384

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

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.",

keywords = "B7-H1, Breast cancer, Immunoresistance, PI(3) kinase, Prostate cancer, T cell",

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

note = "Funding Information: 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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AU - Xu, H.

AU - Chen, L.

AU - Simko, J. P.

AU - Waldman, F. M.

AU - Pieper, R. O.

AU - Parsa, A. T.

N1 - Funding Information: 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.

PY - 2009/1/15

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N2 - 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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PI(3) kinase is associated with a mechanism of immunoresistance in breast and prostate cancer

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