Histamine Promotes the Development of Monocyte-Derived Dendritic Cells and Reduces Tumor Growth by Targeting the Myeloid NADPH Oxidase

摘要: The efficiency of immune-mediated clearance cancer cells is hampered by immunosuppressive mediators in the malignant microenvironment, including NADPH oxidase–derived reactive oxygen species. We aimed at defining effects histamine, an inhibitor myeloid oxidase/NOX2, on development Ag-presenting dendritic (DCs) from precursors and impact these mechanisms for tumor growth. Histamine was found to promote maturation human DCs monocytes increasing expression HLA-DR costimulatory molecules, which resulted improved induction Th with Th0 polarity. Experiments using wild-type NOX2-deficient myelomonoblastic showed that histamine facilitated cell only capable generating Treatment mice reduced growth murine EL-4 lymphomas parallel increment tumor-infiltrating NOX2-sufficient but not (gp91phox−/−) mice. propose strategies target oxidase may facilitate endogenous cancer.