Inhibition of breast cancer metastasis by resveratrol-mediated inactivation of tumor-evoked regulatory B cells

Catalina Lee Chang, Monica Bodogai, Alejandro Martin-Montalvo, Katarzyna Wejksza, Mitesh Sanghvi, Ruin Moaddel, Rafael De Cabo, Arya Biragyn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4141-4151
Number of pages11
JournalJournal of Immunology
Volume191
Issue number8
DOIs
StatePublished - Oct 15 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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