title: B cells contribute to the antitumor activity of CpG-oligodeoxynucleotide in a mouse model of metastatic lung carcinoma.
abstract: BACKGROUND
  CpG-oligodeoxynucleotide (CpG-ODN; CpG), a Toll-like receptor-9 ligand, has been widely studied as a potential antitumor adjuvant. Toll-like receptor-9 is highly expressed on lung carcinoma tissues and some immune cells, such as plasmacytoid dendritic cells and B cells.
  
  
  OBJECTIVE
  The aim of our study was to elucidate the effect of CpG on B cells in a mouse model of lung carcinoma.
  
  
  METHODS
  C57Bl/6j, B cell-deficient, and Nude mice were intravenously implanted with the lung metastatic B16-F10 melanoma cells and killed 3 and 7 days after CpG administration.
  
  
  RESULTS
  Administration of CpG increased lung tumor growth in B16-F10-implanted C57BL/6J mice. The genetic absence of B cells strongly facilitated CpG-induced tumor progression. In contrast, the adoptive transfer of CpG-activated B cells induced tumor arrest, associated with a reduced suppressive immune environment due to the lower recruitment of regulatory T cells, myeloid-derived suppressor cells, and CD8(+) regulatory T cells along with the reduced expression of suppressive cytokines such as IL-10 and transforming growth factor-β. Furthermore, concomitant with higher production of IFN-γ, the apoptosis rate in the lungs of mice adoptively transferred with CpG-activated B cells was increased. Depletion of mature CD20(+) B cells increased the lung tumor burden in CpG-treated C57BL/6J mice and nude mice. Moreover, nude mice had the same lung tumor burden as B cell-deficient mice when mature CD20(+) B cells were depleted.
  
  
  CONCLUSIONS
  Our data demonstrate the protective antitumor activity of CpG-activated B cells and shed light on CpG as an antitumor adjuvant for lung cancer therapy.
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: Giovanni
authors.initials: G
authors.lastname: Forte
authors.forename: Antonella
authors.initials: A
authors.lastname: Montinaro
authors.forename: Genoveffa
authors.initials: G
authors.lastname: De Vita
authors.forename: Antonio
authors.initials: A
authors.lastname: Luciano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palma
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Piera
authors.initials: P
authors.lastname: Maiolino
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9