Lactate secreted by cervical cancer cells modulates macrophage phenotype

• DOI: 10.1002/jlb.3a0718-274rr
• Publication Date: 2019-02-27T18:54:16Z
• Authors: Simone Cardozo Stone; Renata Ariza Marq...; Karla Lucia Ferna...; Jesus Paula Carvalho; Paulo Francisco R...; Edmund Chada Baracat; Maricy Tacla; Enrique Boccardo; Kaori Yokochi; Noely Paula Lorenzi; Ana Paula Lepique
• Keywords: Lactate dehydrogenase A

Cervical cancer continues to be a public health problem in developing countries. Previous studies have shown that cervical cells display markers of aerobic glycolysis, indicating these tumors are likely secrete lactate. Mostly, lactate is recognized as molecule capable suppressing immune responses, through inhibition T cells, Mϕs, and dendritic cells. We others previously Mϕs frequent infiltrating cancers with the ability inhibit antitumor responses promote tumor growth angiogenesis. Here, we tested hypothesis lactate, secreted by can modulate Mϕ phenotype. First, showed higher plasma concentrations patients increasing lesion grades, maximum concentration patients, which supported our hypothesis. then inhibited production cell spheroids established from derived lines, using dehydrogenase inhibitor, oxamate, prior co-culture monocytes. Lactate mediated part crosstalk between promoting secretion IL-1β, IL-10, IL-6, up-regulation hypoxia induced factor-1α expression, down-regulation p65-NFκB phosphorylation Mϕs. also co-cultures treated oxamate were better inducers activation. Of note, experiments performed monocarboxylate transporters rendered similar results. Our data confirms influences phenotype suppressive