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Accession IconGSE43278

Cancer-produced metabolites of 5-lipoxygenase induce tumor-evoked Bregs via peroxisome proliferator-activated receptor alpha

Organism Icon Mus musculus
Sample Icon 16 Downloadable Samples
Technology Badge IconVUmc/Illumina Sentrix MouseRef8 v1.1

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Breast cancer cells facilitate distant metastasis through the induction of immunosuppressive regulatory B cells, designated tBregs. We report here that, to do this, breast cancer cells produce metabolites of the 5-lipoxygenase (5-LO) pathway such as leukotriene B4 (LTB4) to activate the proliferator-activated receptor alpha (PPARalpha) in B cells. Inactivation of LTB4 signaling or genetic deficiency of PPARalpha 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, PPARalpha initiates programs required for differentiation of tBregs. We propose that PPARalpha in B cells or/and tumor 5-LO pathways represents new targets for pharmacological control of tBreg-mediated cancer escape.
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