title: Histamine promotes the development of monocyte-derived dendritic cells and reduces tumor growth by targeting the myeloid NADPH oxidase.
abstract: The efficiency of immune-mediated clearance of cancer cells is hampered by immunosuppressive mediators in the malignant microenvironment, including NADPH oxidase-derived reactive oxygen species. We aimed at defining the effects of histamine, an inhibitor of the myeloid NADPH oxidase/NOX2, on the development of Ag-presenting dendritic cells (DCs) from myeloid precursors and the impact of these mechanisms for tumor growth. Histamine was found to promote the maturation of human DCs from monocytes by increasing the expression of HLA-DR and costimulatory molecules, which resulted in improved induction of Th cells with Th0 polarity. Experiments using wild-type and NOX2-deficient myelomonoblastic cells showed that histamine facilitated myeloid cell maturation only in cells capable of generating reactive oxygen species. Treatment of mice with histamine reduced the growth of murine EL-4 lymphomas in parallel with an increment of tumor-infiltrating DCs in NOX2-sufficient mice but not in NOX2-deficient (gp91(phox) (-/-)) mice. We propose that strategies to target the myeloid NADPH oxidase may facilitate the development of endogenous DCs in cancer.
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden anna.martner@gu.se.
authors: Anna
authors: A
authors: Martner
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors: Hanna G
authors: HG
authors: Wiktorin
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors: Brianna
authors: B
authors: Lenox
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors: Frida
authors: F
authors: Ewald Sander
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors: Ebru
authors: E
authors: Aydin
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors: Johan
authors: J
authors: Aurelius
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors: Fredrik B
authors: FB
authors: Thorén
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors: Anders
authors: A
authors: Ståhlberg
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors: Svante
authors: S
authors: Hermodsson
authors: Sahlgrenska Cancer Center, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors: Kristoffer
authors: K
authors: Hellstrand
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D006632:Histamine / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D019255:NADPH Oxidases / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D006632:Histamine; D019255:NADPH Oxidases