Cancer-produced metabolites of 5-lipoxygenase induce tumor-evoked regulatory B Cells via peroxisome proliferator-activated receptor α

Katarzyna Wejksza, Catalina Lee Chang, Monica Bodogai, Jessica Bonzo, Frank J. Gonzalez, Elin Lehrmann, Kevin Becker, Arya Biragyn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Breast cancer cells facilitate distant metastasis through the induction of immunosuppressive regulatory B cells, designated tBregs. We report in this study that, to do this, breast cancer cells produce metabolites of the 5-lipoxygenase pathway such as leukotriene B4 to activate the peroxisome proliferator- activated receptor a (PPARa) in B cells. Inactivation of leukotriene B4 signaling or genetic deficiency of PPARa in B cells blocks the generation of tBregs and thereby abrogates lung metastasis in mice with established breast cancer. Thus, in addition to eliciting fatty acid oxidation and metabolic signals, PPARa initiates programs required for differentiation of tBregs. We propose that PPARa in B cells and/or tumor 5-lipoxygenase pathways represents new targets for pharmacological control of tBreg-mediated cancer escape.

Original languageEnglish (US)
Pages (from-to)2575-2584
Number of pages10
JournalJournal of Immunology
Volume190
Issue number6
DOIs
StatePublished - Mar 15 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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