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

• Published in: Immunity (Cambridge, Mass.) Vol. 35; no. 1; p. 123
• Main Authors: Donkor, Moses K, Sarkar, Abira, Savage, Peter A, Franklin, Ruth A, Johnson, Linda K, Jungbluth, Achim A, Allison, James P, Li, Ming O
• Format: Journal Article
• Language: English
• Published: Cambridge Elsevier Limited 22.07.2011
• Subjects: Antigens; Immune system; Kinases; Lymphoma; Rodents; T cell receptors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2011.04.019

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-β is implicated in immunosuppression, but the cellular mechanism by which TGF-β 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-β signaling in T cells from the tumor-draining lymph nodes. Blockade of TGF-β 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-β1 was sufficient to augment T cell cytotoxic activity and blocked tumor growth and metastases. These findings reveal that T cell production of TGF-β1 is an essential requirement for tumors to evade immunosurveillance independent of TGF-β produced by tumors.