title: Plasmacytoid dendritic cells alter the antitumor activity of CpG-oligodeoxynucleotides in a mouse model of lung carcinoma.
abstract: The effect of CpG-oligodeoxynucleotides (CpG) has been studied on a number of tumors. Although CpG may facilitate tumor regression in mouse models of melanoma, its activity in lung cancer is unclear. The aim of our study was to elucidate the effect of CpG (0.5-50 μg/mouse) in a mouse model of Lewis lung carcinoma cell-induced lung cancer. Lung tumor growth increased at 3 and 7 d after a single administration of CpG. This was associated with a greater influx of plasmacytoid dendritic cells (pDCs), immature myeloid dendritic cells, and greater recruitment of regulatory T cells. Depletion of pDCs using a specific Ab (m927) reversed the immune-suppressive environment and resulted in a decreased lung tumor burden, accompanied by a greater influx of active myeloid dendritic cells and CD8(+) T cells, and a higher production of Th1- and Th17-like cytokines. Furthermore, the rate of apoptosis in the lungs of mice treated with CpG increased following the depletion of pDCs. CpG treatment alone does not lead to tumor regression in the lung. However, ablation of pDCs renders CpG a good adjuvant for lung cancer chemotherapy in this experimental model.
authors.affiliation: Department of Pharmaceutical Science, University of Salerno, Fisciano, Italy. rosalinda.sorrentino@googlemail.com
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Silvana
authors.initials: S
authors.lastname: Morello
authors.forename: Antonio
authors.initials: A
authors.lastname: Luciano
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Crother
authors.forename: Piera
authors.initials: P
authors.lastname: Maiolino
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonavita
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.forename: Moshe
authors.initials: M
authors.lastname: Arditi
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000276:immunology*; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides