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

Rosalinda Sorrentino, Silvana Morello, Giovanni Forte, Antonella Montinaro, Genoveffa De Vita, Antonio Luciano, Giuseppe Palma, Claudio Arra, Piera Maiolino, Ian M. Adcock, Aldo Pinto

Research output: Contribution to journalArticle

Abstract

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 + Bcells 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.

Original languageEnglish
Pages (from-to)1369-1379
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume183
Issue number10
DOIs
Publication statusPublished - May 15 2011

Keywords

  • CpG
  • Immune-suppressive environment
  • Lung carcinoma
  • Tumor immunity

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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