title: T cell surveillance of oncogene-induced prostate cancer is impeded by T cell-derived TGF-β1 cytokine.
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-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.
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Moses K
authors.initials: MK
authors.lastname: Donkor
authors.forename: Abira
authors.initials: A
authors.lastname: Sarkar
authors.forename: Peter A
authors.initials: PA
authors.lastname: Savage
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Franklin
authors.forename: Linda K
authors.initials: LK
authors.lastname: Johnson
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
authors.forename: Ming O
authors.initials: MO
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance; D007157:Immunologic Surveillance; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes / Q000502:physiology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019139:Tumor Escape
chemical_list: D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta