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

Valeria P. Makarenkova, Galina V. Shurin, Irina L. Tourkova, Levent Balkir, Georgi Pirtskhalaishvili, Lori Perez, Valentin Gerein, Jill M. Siegfried, Michael R. Shurin

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34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)55-67
Number of pages13
JournalJournal of Neuroimmunology
Volume145
Issue number1-2
DOIs
StatePublished - Dec 2003

Keywords

  • Bombesin-like peptides
  • Dendritic cells
  • Small cell lung carcinoma

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    Makarenkova, V. P., Shurin, G. V., Tourkova, I. L., Balkir, L., Pirtskhalaishvili, G., Perez, L., Gerein, V., Siegfried, J. M., & Shurin, M. R. (2003). Lung cancer-derived bombesin-like peptides down-regulate the generation and function of human dendritic cells. Journal of Neuroimmunology, 145(1-2), 55-67. https://doi.org/10.1016/j.jneuroim.2003.09.009