Lung cancer-derived bombesin-like peptides down-regulate the generation and function of human dendritic cells

J Neuroimmunol. 2003 Dec;145(1-2):55-67. doi: 10.1016/j.jneuroim.2003.09.009.


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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen Presentation
  • Bombesin / metabolism
  • Bombesin / pharmacology*
  • Cell Differentiation / immunology
  • Cell Line, Tumor
  • Cell Survival / immunology
  • Cells, Cultured
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dose-Response Relationship, Immunologic
  • Down-Regulation* / immunology
  • Endocytosis / immunology
  • Gastrin-Releasing Peptide / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / biosynthesis
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / pharmacology*
  • Neurokinin B / analogs & derivatives*
  • Neurokinin B / biosynthesis
  • Neurokinin B / genetics
  • RNA, Messenger / biosynthesis
  • Receptors, Bombesin / biosynthesis
  • Receptors, Bombesin / genetics


  • Immunosuppressive Agents
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, Bombesin
  • Interleukin-12
  • Gastrin-Releasing Peptide
  • Neurokinin B
  • neuromedin B
  • Bombesin