B cells contribute to the antitumor activity of CpG-oligodeoxynucleotide in a mouse model of metastatic lung carcinoma

Am J Respir Crit Care Med. 2011 May 15;183(10):1369-79. doi: 10.1164/rccm.201010-1738OC. Epub 2011 Jan 28.


Rationale: 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.

Objectives: 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.

Measurements and main 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / pharmacology*
  • Analysis of Variance
  • Animals
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Oligodeoxyribonucleotides / genetics
  • Oligodeoxyribonucleotides / immunology*
  • Oligodeoxyribonucleotides / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology*


  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides
  • Toll-Like Receptor 9