Original Article

Subject Categories: Tumor Biology

Journal of Investigative Dermatology (2004) 123, 395–402; doi:10.1111/j.0022-202X.2004.23233.x

Peritumoral CpG Oligodeoxynucleotide Treatment Inhibits Tumor Growth and Metastasis of B16F10 Melanoma Cells

Nagisa Kunikata*, Kunio Sano, Motoko Honda*, Kuniaki Ishii, Jun Matsunaga*, Ryuhei Okuyama*, Kazuhiro Takahashi*, Hiroshi Watanabe*, Gen Tamura, Hachiro Tagami* and Tadashi Terui*

  1. *Department of Dermatology, Tohoku University, Graduate School of Medicine, Sendai, Japan
  2. Department of Respiratory and Infectious Diseases, Tohoku University, Graduate School of Medicine, Sendai, Japan
  3. Department of Pharmacology, Yamagata University School of Medicine, Yamagata, Japan

Correspondence: Tadashi Terui, Department of Dermatology, Tohoku University Graduate School of Medicine, Seiryo-machi 1-1, Aoba-ku 980-8574, Sendai, Japan. Email: terui@mail.tains.tohoku.ac.jp

Received 26 January 2004; Revised 17 March 2004; Accepted 1 April 2004; Published online 6 July 2004.

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Abstract

Although melanoma mostly affects the skin, it is notorious for its propensity to easily develop metastasis. Metastatic melanoma is highly resistant to a variety of therapies. We examined the anti-metastatic potential of peritumoral monotherapy against murine cutaneous B16F10 melanoma with synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs. We demonstrated that repeated peritumoral injections of CpG ODN significantly reduced skin tumor size. Peritumoral CpG ODN-treatment of skin tumors prevented the development of pulmonary B16F10 colonies. Adoptive transfer of splenocytes obtained from CpG ODN-treated mice markedly reduced the number of previously established pulmonary colonies in recipient naïve mice. T-lymphocyte depletion studies indicated that the anti-metastatic effect was dependent on both CD4+ and CD8+ T cells. These results suggest that CpG ODN are promising as a preventive and therapeutic anti-metastatic measure against melanoma.

Keywords:

cancer immunotherapy, CD4+ T cell, CD8+ T cell, CpG motif, CTL

Abbreviations:

Ag, antigen; CTL, cytotoxic T lymphocyte; DCs, dendritic cells; IFN, interferon; IL, interleukin; NK, natural killer; ODN, oligodeoxynucleotide; PBS, phosphate-buffered saline; Th, T helper; TLR, Toll-like receptor; TUNEL, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling

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