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T Cell Surveillance of Oncogene-Induced Prostate Cancer Is Impeded by T Cell-Derived TGF-beta 1 Cytokine

By Moses K. Donkor, Abira Sarkar, Peter A. Savage, Ruth A. Franklin, Linda K. Johnson, Achim A. Jungbluth, James P. Allison and Ming O. Li

Abstract

Tolerance induction in T cells takes place in most tumors and is thought to account for tumor evasion from immune eradication. Production of the cytokine TGF-beta is implicated in immunosuppression, but the cellular mechanism by which TGF-beta induces T cell dysfunction remains unclear. With a transgenic model of prostate cancer, we showed that tumor development was not suppressed by the adaptive immune system, which was associated with heightened TGF-beta signaling in T cells from the tumor-draining lymph nodes. Blockade of TGF-beta signaling in T cells enhanced tumor antigen-specific T cell responses and inhibited tumor development. Surprisingly, T cell- but not Treg cell-specific ablation of TGF-beta 1 was sufficient to augment T cell cytotoxic activity and blocked tumor growth and metastases. These findings reveal that T cell production of TGF-beta 1 is an essential requirement for tumors to evade immunosurveillance independent of TGF-beta produced by tumors

Publisher: Cell Press
Year: 2011
DOI identifier: 10.1016/j.immuni.2011.04.019
OAI identifier: oai:researchonline.jcu.edu.au:33169
Provided by: ResearchOnline@JCU
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