IFN-producing killer dendritic cells contribute to the inhibitory effect of poly I:C on the progression of murine melanoma
IFN-producing killer dendritic cells contribute to the inhibitory effect of poly I:C on the progression of murine melanoma
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DOI：
10.1097/cji.0b013e31817d8e75
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发表时间：
2008-07-01
影响因子：
3.9
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
--
作者：
Jiang, Qun;Wei, Haiming;Tian, Zhigang
Toll样受体3激动剂多聚肌苷多胞苷(Poly I：C)已被广泛应用于肿瘤免疫治疗。本研究通过自然杀伤细胞(NK细胞)和干扰素(干扰素)-γ依赖的方式，证明了腹腔注射POOL I：C能抑制B16黑色素瘤细胞在C57BL/6小鼠体内的肺和肝转移，从而延长小鼠的存活时间。B220(+)CD11c(+)NK1.1(+)细胞是最近被定义为产生干扰素的杀伤树突状细胞(IKDC)，在经PolyI：C治疗的荷瘤小鼠的脾、肺和肝脏中，与对照组相比显著增加。在这个独特的NK细胞亚群中，Poly I：C诱导的干扰素-γ表明它在该模型的肿瘤抑制中起到了关键作用。同时，体外培养实验结果表明，Poly I：C与B16细胞协同作用能显著促进不同器官淋巴细胞对IKDC的扩增，同时产生干扰素。此外，体外扩增的IKDC与常规NK细胞一样，对B16细胞和YAC-1细胞也具有杀伤活性。综上所述，本研究结果对干扰素-γ和IKDC在PolyI：C抗肿瘤作用中的作用提供了新的见解，并可能有助于解释为什么PolyI：C可能作为佐剂来提高固有细胞的抗肿瘤效果。
Toll-like receptor 3 agonist polyinosinic-polycytidilic acid (poly I:C) has been widely used as a potent adjuvant in tumor immunotherapy. In the present study, it was demonstrated that intraperitoneal injection of pole I:C could inhibit lung and liver metastasis of B16 melanoma cells in C57BL/6 mice in natural killer (NK) cells and interferon (IFN)-gamma dependent manner, leading to prolonged survival of the mice. B220(+) CD11c(+) NK1.1(+) cells, recently defined as IFN-producing killer dendritic cells (IKDCs) were markedly increased in the spleen, lung, and liver of poly I:C-treated tumor bearing mice, compared with the control group. IFN-gamma induction by poly I:C in this unique NK cell subset indicated its critical contribution in tumor suppression in this model. Meanwhile, results of in vitro culture assay showed that poly I:C synergized with B16 cells could significantly promote IKDCs expansion in lymphocytes from different organs along with IFN production. Moreover, these ex vivo expanded IKDCs also exerted cytolytic activities against B16 cells and YAC-1 cells as conventional NK cells did. In conclusion, the findings of this study provide new insights into the role of IFN-gamma and IKDCs in the antitumor effect of poly I:C, and will possibly be helpful to explain why poly I:C may work as an adjucant to improve the antitumor effects of innate cells.