TY - JOUR
T1 - Lung cancer-derived bombesin-like peptides down-regulate the generation and function of human dendritic cells
AU - Makarenkova, Valeria P.
AU - Shurin, Galina V.
AU - Tourkova, Irina L.
AU - Balkir, Levent
AU - Pirtskhalaishvili, Georgi
AU - Perez, Lori
AU - Gerein, Valentin
AU - Siegfried, Jill M.
AU - Shurin, Michael R.
N1 - Funding Information:
This work was supported by RO1 CA80126 (M.R.S.), RO1 CA84270 (M.R.S.) and NCI Lung Cancer SPORE grant P50 CA090440 (J.M.S.).
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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.
KW - Bombesin-like peptides
KW - Dendritic cells
KW - Small cell lung carcinoma
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U2 - 10.1016/j.jneuroim.2003.09.009
DO - 10.1016/j.jneuroim.2003.09.009
M3 - Article
C2 - 14644031
AN - SCOPUS:0344872718
SN - 0165-5728
VL - 145
SP - 55
EP - 67
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -