Activated natural killer cell-mediated immunity is required for the inhibition of tumor metastasis by dendritic cell vaccination
Activated natural killer cell-mediated immunity is required for the inhibition of tumor metastasis by dendritic cell vaccination
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DOI：
10.1038/emm.2004.55
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发表时间：
2004-10-31
影响因子：
12.8
通讯作者：
Lim, JS
中科院分区：
文献类型：
--
作者：
Kim, A;Noh, YW;Lim, JS
肿瘤抗原致敏的树突状细胞（DCs）可激活肿瘤特异性细胞毒性T淋巴细胞（CTL），参与肿瘤的保护和消退。在这项研究中，我们研究了坏死肿瘤裂解物脉冲（DC）是否可以有效地防止恶性黑色素瘤肿瘤细胞转移到肺。发现来自小鼠骨髓的DC在用肿瘤裂解物脉冲后产生显著升高水平的IL-12。此外，用这些DC免疫诱导CTL活化并保护小鼠免受静脉接种肿瘤细胞的转移发展。此外，这些DC在体外以接触依赖的方式激活NK细胞，并在体内诱导NK活性。此外，在DC疫苗接种前NK细胞耗竭显著降低了肿瘤特异性CTL活性、IFN-γ产生和IFN-γ诱导的基因表达，并最终干扰了肿瘤脉冲DC的抗肿瘤作用。最后，在严重缺乏NK细胞的细胞溶解活性的C57 BU 6 J-bglbg小鼠中获得了关于NK细胞依赖性的类似发现。这些数据表明，至少在B16黑色素瘤模型中，DC疫苗接种引起的抗肿瘤作用需要溶细胞NK细胞和CD 8（+）T细胞的参与。本研究结果将为肿瘤免疫治疗中DC疫苗的有效设计提供重要数据。
Immunization with dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL), which is responsible for tumor protection and regression. In this study, we examined whether (DCs) pulsed with necrotic tumor lysates can efficiently prevent malignant melanoma tumor cell metastasis to the lung. DCs derived from mouse bone marrow were found to produce remarkably elevated levels of IL-12 after being pulsed with the tumor lysates. Moreover, immunization with these DCs induced CTL activation and protected mice from metastasis development by intravenously inoculated tumor cells. In addition, these DCs activated NK cells in vitro in a contact-dependent manner, and induced NK activities in vivo. Furthermore, NK cell depletion before DC vaccination significantly reduced the tumor-specific CTL activity, IFN-gamma production, and IFN-gamma-inducible gene expression, and eventually interfered with the antitumor effect of tumor-pulsed DCs. Finally, similar findings with respect to NK cell dependency were obtained in the C57BU 6J-bglbg mice, which have severe deficiency in cytolytic activity of NK cells. These data suggest that the antitumor effect elicited by DC vaccination, at least in a B16 melanoma model, requires the participation of both cytolytic NK and CD8(+) T cells. The findings of this study would provide important data for the effective design of DC vaccines for cancer immunotherapy.