T cell- but not tumor cell-produced TGF-β1 promotes the development of spontaneous mammary cancer
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1 Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Received: December 22, 2011; Accepted: December 23, 2011; Published: December 31, 2011;
Keywords: TGF-β, T cell tolerance, immunosurveillance, tumor immunity, metastasis, immunotherapy
Dr. Ming O. Li, email:
During their development, tumors acquire multiple capabilities that enable them to proliferate, disseminate and evade immunosurveillance. A putative mechanism is through the production of the cytokine TGF-β1. We showed in our recent studies that T cell-produced TGF-β1 inhibits antitumor T cell responses to foster tumor growth raising the question of the precise function of TGF-β1 produced by tumor cells in tumor development. Here, using a transgenic model of mammary cancer, we report that deletion of TGF-β1 from tumor cells did not protect mice from tumor development. However, ablation of TGF-β1 from T cells significantly inhibited mammary tumor growth. Additionally, absence of TGF-β1 in T cells prevented tumors from advancing to higher pathological grades and further suppressed secondary tumor development in the lungs. These findings reveal T cells but not tumor cells as a critical source of TGF-β1 that promotes tumor development.
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