Natural killer cell is a major producer of interferon γ that is critical for the IL-12-induced anti-tumor effect in mice
Natural killer cell is a major producer of interferon γ that is critical for the IL-12-induced anti-tumor effect in mice
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DOI：
10.1007/s00262-009-0764-x
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发表时间：
2010-03-01
影响因子：
5.8
通讯作者：
Hayashi, Norio
中科院分区：
文献类型：
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作者：
Uemura, Akio;Takehara, Tetsuo;Hayashi, Norio
虽然IL-12的抗肿瘤作用主要由IFN γ介导，但尚未清楚地确定哪种细胞类型最有效地产生IFN γ并因此引发或促进IL-12的抗肿瘤作用。在本研究中，我们证明了IL-12基因的流体动力学注射导致野生型小鼠中的CT-26结肠癌细胞的IFN-γ产生延长，NK细胞活化和肝转移的完全抑制，但在IFN-γ敲除小鼠中没有。与非NK细胞相比，NK细胞表达更高水平的STAT 4，并且在IL-12施用后显示出更强的STAT 4磷酸化和IFN γ产生。将野生型NK细胞连续转移到IFN γ敲除小鼠中恢复了IL-12诱导的IFN γ产生、NK细胞活化和抗肿瘤作用，而转移相同数量的野生型非NK细胞则没有。总之，NK细胞是IFN γ的主要生产者，IFN γ对IL-12抗肿瘤治疗至关重要。
Although the anti-tumor effect of IL-12 is mediated mostly by IFN gamma, which cell types most efficiently produce IFN gamma and therefore initiate or promote the anti-tumor effect of IL-12 has not been clearly determined. In the present study, we demonstrated hydrodynamic injection of the IL-12 gene led to prolonged IFN gamma production, NK-cell activation and complete inhibition of liver metastasis of CT-26 colon cancer cells in wild-type mice, but not in IFN gamma knockout mice. NK cells expressed higher levels of STAT4 and upon IL-12 administration displayed stronger STAT4 phosphorylation and IFN gamma production than non-NK cells. Adoptive transfer of wild-type NK cells into IFN gamma knockout mice restored IL-12-induced IFN gamma production, NK-cell activation and anti-tumor effect, whereas transfer of the same number of wild-type non-NK cells did not. In conclusion, NK cells are predominant producers of IFN gamma that is critical for IL-12 anti-tumor therapy.