Abstract
Development of tumors is regulated by tumor-derived neuroendocrine factors, including bombesin-like peptides (BLP). We have evaluated neuroendocrine regulation of dendritic cell (DC) maturation and function by both tumor-derived and purified bombesin (BOM), neuromedin B (NMB), gastrin-releasing peptide (GRP), and a BOM antagonist D-Phe-bombesin (DPB). BOM, NMB and GRP dose-dependently inhibited maturation of DC assessed as down-regulation of CD40, CD80 and CD86 expression on DC. BOM and GRP also inhibited interleukin-12 (IL-12) production by DC and their ability to activate T cells. DPB partly abrogated immunosuppressive effect of tumor cells on DC. These data are a first evidence for the role of BLP in the regulation of DC maturation and function, demonstrating that BLP inhibit DC maturation and longevity in the lung cancer microenvironment. This suggests a new mechanism of tumor escape and provides new targets for the immunopharmacological correction of immune effectors in cancer.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigen Presentation
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Bombesin / metabolism
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Bombesin / pharmacology*
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Cell Differentiation / immunology
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Cell Line, Tumor
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Cell Survival / immunology
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Cells, Cultured
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Dendritic Cells / cytology*
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dose-Response Relationship, Immunologic
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Down-Regulation* / immunology
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Endocytosis / immunology
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Gastrin-Releasing Peptide / metabolism
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Humans
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Immunosuppressive Agents / pharmacology*
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Interleukin-12 / antagonists & inhibitors
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Interleukin-12 / biosynthesis
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Lung Neoplasms / immunology
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Lung Neoplasms / metabolism*
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / pharmacology*
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Neurokinin B / analogs & derivatives*
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Neurokinin B / biosynthesis
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Neurokinin B / genetics
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RNA, Messenger / biosynthesis
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Receptors, Bombesin / biosynthesis
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Receptors, Bombesin / genetics
Substances
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Immunosuppressive Agents
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Neoplasm Proteins
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RNA, Messenger
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Receptors, Bombesin
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Interleukin-12
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Gastrin-Releasing Peptide
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Neurokinin B
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neuromedin B
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Bombesin