Abstract
We reported previously that tumor-evoked regulatory B cells (tBregs) play an essential role in breast cancer lung metastasis by inducing TGF-β-dependent conversion of metastasis-promoting Foxp3(+) regulatory T cells (Tregs). In this article, we show that resveratrol (RSV), a plant-derived polyphenol, at low and noncytotoxic doses for immune cells, can efficiently inhibit lung metastasis in mice. The mechanism of this process is that RSV inactivates Stat3, preventing the generation and function of tBregs, including expression of TGF-β. As a result, it frees antitumor effector immune responses by disabling tBreg-induced conversion of Foxp3(+) Tregs. We propose that low doses of RSV may also benefit humans by controlling cancer escape-promoting tBregs/Tregs without nonspecific inactivation of effector immune cells.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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B-Lymphocytes, Regulatory / drug effects*
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Female
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Forkhead Transcription Factors / metabolism
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Lung Neoplasms / drug therapy
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Lung Neoplasms / immunology
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Lung Neoplasms / prevention & control*
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Lung Neoplasms / secondary
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Mammary Neoplasms, Animal / drug therapy*
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Mammary Neoplasms, Animal / immunology
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Mammary Neoplasms, Animal / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Resveratrol
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STAT3 Transcription Factor / drug effects
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STAT3 Transcription Factor / metabolism
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Stilbenes / therapeutic use*
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T-Lymphocytes, Regulatory / immunology*
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Transforming Growth Factor beta / biosynthesis
Substances
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Stilbenes
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Transforming Growth Factor beta
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Resveratrol