Kunikata Nagisa, Sano Kunio, Honda Motoko, Ishii Kuniaki, Matsunaga Jun, Okuyama Ryuhei, Takahashi Kazuhiro, Watanabe Hiroshi, Tamura Gen, Tagami Hachiro, Terui Tadashi
Department of Dermatology, tOHOKU University, Graduate School of Medicine, Sendai, Japan.
J Invest Dermatol. 2004 Aug;123(2):395-402. doi: 10.1111/j.0022-202X.2004.23233.x.
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.
尽管黑色素瘤主要影响皮肤,但它因易于发生转移而声名狼藉。转移性黑色素瘤对多种治疗具有高度抗性。我们用含有未甲基化CpG基序的合成寡脱氧核苷酸(ODN)研究了瘤周单一疗法对小鼠皮肤B16F10黑色素瘤的抗转移潜力。我们证明,重复瘤周注射CpG ODN可显著减小皮肤肿瘤大小。对皮肤肿瘤进行瘤周CpG ODN治疗可预防肺B16F10集落的形成。从CpG ODN处理的小鼠获得的脾细胞的过继转移显著减少了受体未致敏小鼠中先前建立的肺集落数量。T淋巴细胞耗竭研究表明,抗转移作用依赖于CD4 +和CD8 + T细胞。这些结果表明,CpG ODN作为一种针对黑色素瘤的预防性和治疗性抗转移措施具有前景。