title: Cancer-produced metabolites of 5-lipoxygenase induce tumor-evoked regulatory B cells via peroxisome proliferator-activated receptor α.
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 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.
authors: Immunoregulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224, USA.
authors: Katarzyna
authors: K
authors: Wejksza
authors: Catalina
authors: C
authors: Lee-Chang
authors: Monica
authors: M
authors: Bodogai
authors: Jessica
authors: J
authors: Bonzo
authors: Frank J
authors: FJ
authors: Gonzalez
authors: Elin
authors: E
authors: Lehrmann
authors: Kevin
authors: K
authors: Becker
authors: Arya
authors: A
authors: Biragyn
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D008084:Lipoxygenase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology
chemical_list: D047493:PPAR alpha; D008084:Lipoxygenase