Cancer-produced metabolites of 5-lipoxygenase induce tumor-evoked regulatory B cells via peroxisome proliferator–activated receptor α
K Wejksza, C Lee-Chang, M Bodogai… - The Journal of …, 2013 - journals.aai.org
The Journal of Immunology, 2013•journals.aai.org
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 B 4 to activate
the peroxisome proliferator–activated receptor α (PPARα) in B cells. Inactivation of
leukotriene B 4 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 …
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 B 4 to activate
the peroxisome proliferator–activated receptor α (PPARα) in B cells. Inactivation of
leukotriene B 4 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 …
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 B 4 to activate the peroxisome proliferator–activated receptor α (PPARα) in B cells. Inactivation of leukotriene B 4 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.
journals.aai.org