IL-12/15/18引发自然杀伤细胞对肝细胞癌的活性

StephenW

Hepatology International

January 2019, Volume 13, Issue 1, pp 75–83 | Cite as
Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma

    Authors
    Authors and affiliations

    Lihui ZhuangRebecca J. FultonPauline RettmanA. Emre SayanJonathan CoadAymen Al-ShamkhaniSalim I. KhakooEmail author

    Lihui Zhuang
        1
    Rebecca J. Fulton
        1
    Pauline Rettman
        1
    A. Emre Sayan
        1
    Jonathan Coad
        1
    Aymen Al-Shamkhani
        1
    Salim I. Khakoo
        1Email authorView author's OrcID profile

    1.Faculty of Medicine, Southampton General HospitalUniversity of SouthamptonSouthamptonUK

Open Access
Original Article
First Online: 22 November 2018

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Abstract
Background

Hepatocellular carcinoma (HCC) is common, but remains difficult to treat. Natural killer (NK) cells are cells of the innate immune system that have potent anti-cancer activity. Recent work has shown that stimulation with IL-12/15/18 leads to the generation of NK cells with enhanced functional and putative “memory” properties. We have investigated the activity of these NK cells against HCC cell lines in vitro and in a mouse model.
Methods

NK cells from healthy donors or individuals with HCC were activated with IL-12/15/18 in vitro and tested for cytotoxic activity against a panel of human HCC cell lines. IL-12/15/18 primed murine NK cells were then infused into a murine model of spontaneously arising HCC to test for anti-tumor activity.
Results

NK cells from patients and healthy controls had similar expression levels of activating and inhibitory NK cell receptors. However, proliferation of NK cells from HCC patients was weaker than healthy controls in response to IL-12/15/18 and IL-2 (p < 0.001 at day 9). In vitro, NK cells from both groups of individuals killed HCC targets to similar levels and this was unrelated to NKG2D expression. In a spontaneous model of HCC, IL-12/15/18 activated NK cells trafficked to the liver and resulted in lower levels of spontaneous HCC formation (p < 0.01).
Conclusion

Cytokine-primed NK cells from patients with HCC have similar levels of activity against HCC cell lines as those from healthy controls. This type of activated NK cell has immunotherapeutic potential against hepatocellular carcinoma.
Keywords
Innate immunity Immunotherapy Cytokines Liver Cancer

StephenW

国际肝病学

2019年1月，第13卷，第1期，第75-83页|引用为
IL-12/15/18引发自然杀伤细胞对肝细胞癌的活性

    作者
    作者和附属机构

    Lihui ZhuangRebecca J. FultonPauline RettmanA。 Emre SayanJonathan CoadAymen Al-ShamkhaniSalim I. KhakooEmail author

    李辉庄
        1
    Rebecca J. Fulton
        1
    Pauline Rettman
        1
    A.埃姆雷萨彦
        1
    乔纳森科德
        1
    Aymen Al-Shamkhani
        1
    Salim I. Khakoo
        1Email authorView作者的OrcID个人资料

    1.南安普顿综合医院医学院南安普顿大学南安普顿分校

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来源文章
首次在线：2018年11月22日

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抽象
背景

肝细胞癌（HCC）很常见，但仍难以治疗。自然杀伤（NK）细胞是先天免疫系统的细胞，具有有效的抗癌活性。最近的研究表明，IL-12/15/18的刺激导致NK细胞的产生，具有增强的功能和推定的“记忆”特性。我们已经在体外和小鼠模型中研究了这些NK细胞对HCC细胞系的活性。
方法

来自健康供体或具有HCC的个体的NK细胞在体外用IL-12/15/18活化，并测试针对一组人HCC细胞系的细胞毒活性。然后将IL-12/15/18引发的鼠NK细胞注入自发产生的HCC的鼠模型中以测试抗肿瘤活性。
结果

来自患者和健康对照的NK细胞具有相似的活化和抑制性NK细胞受体的表达水平。然而，响应于IL-12/15/18和IL-2，来自HCC患者的NK细胞的增殖弱于健康对照（在第9天p <0.001）。在体外，来自两组个体的NK细胞将HCC靶标杀死至相似水平，这与NKG2D表达无关。在自发的HCC模型中，IL-12/15/18激活的NK细胞被贩运到肝脏并导致较低水平的自发性HCC形成（p <0.01）。
结论

来自HCC患者的细胞因子引发的NK细胞具有与来自健康对照的HCC细胞系相似的活性水平。这种类型的活化NK细胞具有抗肝细胞癌的免疫治疗潜力。
关键词
先天免疫免疫疗法细胞因子肝癌

StephenW

https://link.springer.com/articl ... aign=toc_12072_13_1