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

نویسندگان

  • Katarzyna Wejksza
  • Catalina Lee-Chang
  • Monica Bodogai
  • Jessica Bonzo
  • Frank J Gonzalez
  • Elin Lehrmann
  • Kevin Becker
  • Arya Biragyn
چکیده

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 α (PPARα) in B cells. Inactivation of leukotriene B4 signaling or genetic deficiency of PPARα 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, PPARα initiates programs required for differentiation of tBregs. We propose that PPARα in B cells and/or tumor 5-lipoxygenase pathways represents new targets for pharmacological control of tBreg-mediated cancer escape.

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Cancer-Produced Metabolites of 5-Lipoxygenase Induce Tumor-Evoked Regulatory B Cells via Peroxisome Proliferator–Activated Receptor a

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عنوان ژورنال:
  • Journal of immunology

دوره 190 6  شماره 

صفحات  -

تاریخ انتشار 2013