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

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.

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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.

Item ID: 33169
Item Type: Article (Research - C1)
ISSN: 1097-4180
Funders: NIAMS-NIH RO1 grant, NIAMS-NIH KO1 grant, Arthritis Foundation Investigator Award, CRI predoctoral fellowship
Projects and Grants: NIAMS-NIH RO1 grant AR060723, NIAMS-NIH KO1 grant AR053595
Date Deposited: 14 May 2014 09:56
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110316 Pathology (excl Oral Pathology) @ 34%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110709 Tumour Immunology @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110706 Immunogenetics (incl Genetic Immunology) @ 33%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 50%
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