Donkor, Moses K., Sarkar, Abira, Savage, Peter A., Franklin, Ruth A., Johnson, Linda K., Jungbluth, Achim A., Allison, James P., and Li, Ming O. (2011) T Cell Surveillance of Oncogene-Induced Prostate Cancer Is Impeded by T Cell-Derived TGF-beta 1 Cytokine. Immunity, 35 (1). pp. 123-134.

PDF (Published Version) - Published Version Restricted to Repository staff only

 

101

3

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.

Actions (Repository Staff Only)

Item Control Page