Lung cancer-derived bombesin-like peptides down-regulate the generation and function of human dendritic cells.
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.
Makarenkova
Valeria P
VP
Department of Pathology, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Shurin
Galina V
GV
Tourkova
Irina L
IL
Balkir
Levent
L
Pirtskhalaishvili
Georgi
G
Perez
Lori
L
Gerein
Valentin
V
Siegfried
Jill M
JM
Shurin
Michael R
MR
D017951:Antigen Presentation; D001839:Bombesin / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D004705:Endocytosis / Q000276:immunology; D019886:Gastrin-Releasing Peptide / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018004:Receptors, Bombesin / Q000096:biosynthesis / Q000235:genetics
D007166:Immunosuppressive Agents; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D018664:Interleukin-12; D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B; C038393:neuromedin B; D001839:Bombesin