Combination therapy with á-galactosylceramide and a Toll-like receptor agonist exerts an augmented suppressive effect on lung tumor metastasis in a mouse model

Tatsuya Ando, Hiroyasu Ito, Yuko Arioka, Hideyuki Ogiso, Mitsuru Seishima

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

α-galactosylceramide (GalCer), which is a natural killer T (NKT) cell ligand, has been reported to exert therapeutic effects against cancer in humans and mice. Toll-like receptor (TLR) agonists systemically or locally boost antitumor efficacy in mouse cancer models. In our previous study, the co-administration of GalCer and a TLR agonist synergistically enhanced interferon-γ (IFN-γ) production in mouse splenocytes in vitro and in vivo. The increased IFN-γ production promoted a tumor antigen-specific Th1 response. Therefore, co-treatment with GalCer and a TLR agonist is expected to exert an enhanced antitumor effect. In the present study, we examined the effect of GalCer and lipopolysaccharide (LPS) combination therapy in a mouse lung-metastasis model. GalCer and LPS combination therapy markedly decreased the number of lung metastatic tumor nodes. Co-treatment with GalCer and LPS enhanced the mRNA expression of CXCL9 and CXCL10 in mediastinal lymph nodes (MLNs) and increased the number of CD8+ cells in the MLNs. Furthermore, the depletion of CD8+ T cells canceled the antitumor effect of GalCer and LPS combination therapy. Thus, GalCer and LPS combination therapy significantly enhanced tumor antigen-specific immune responses and suppressed tumor growth in a mouse lung-metastasis model.

Original languageEnglish
Pages (from-to)826-832
Number of pages7
JournalOncology reports
Volume33
Issue number2
DOIs
Publication statusPublished - 01-12-2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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