Inhibition of Breast Cancer Metastasis by Resveratrol-Mediated Inactivation of Tumor-Evoked Regulatory B Cells
Inhibition of Breast Cancer Metastasis by Resveratrol-Mediated Inactivation of Tumor-Evoked Regulatory B Cells
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.
- National Institute of Health Pakistan
- Medical Research Council United Kingdom
- MRC Laboratory of Molecular Biology United Kingdom
- National Institutes of Health United States
- National Institute on Aging United States
STAT3 Transcription Factor, B-Lymphocytes, Regulatory, Mice, Inbred BALB C, Lung Neoplasms, Forkhead Transcription Factors, Mammary Neoplasms, Animal, T-Lymphocytes, Regulatory, Mice, Inbred C57BL, Mice, Resveratrol, Transforming Growth Factor beta, Stilbenes, Animals, Female
STAT3 Transcription Factor, B-Lymphocytes, Regulatory, Mice, Inbred BALB C, Lung Neoplasms, Forkhead Transcription Factors, Mammary Neoplasms, Animal, T-Lymphocytes, Regulatory, Mice, Inbred C57BL, Mice, Resveratrol, Transforming Growth Factor beta, Stilbenes, Animals, Female
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