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[白细胞介素-33:抗肿瘤斗争中的朋友还是敌人?]

[Interleukin-33: Friend or Enemy in the Fight against Tumors?].

作者信息

Gorbacheva A M, Mitkin N A

机构信息

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991 Russia.

Immunology Department, Biological Faculty, Moscow State University, Moscow 119234 Russia.

出版信息

Mol Biol (Mosk). 2019 Sep-Oct;53(5):774-789. doi: 10.1134/S0026898419050069.

Abstract

Interleukin-33 (IL-33) belongs to the IL-1 cytokine family and acts as a danger signal. IL-33 is released from stressed or necrotic cells. Initially, IL-33 was described as an inducer of the humoral immune response, which activated Th2 cells and mast cells involved in modulating inflammation and allergic reactions. In addition, IL-33 acts as a stimulator of the Th1, NK, and CD8T cells, which induce a cytotoxic immune response against intracellular pathogens. It was recently discovered that this cytokine is involved in the development of cancer by performing both pro- and antitumor functions. IL-33 can directly affect tumor cells and provokes their proliferation, survival, and metastasis. Moreover, IL-33 stimulates carcinogenesis by remodeling the tumor microenvironment and inducing angiogenesis, thus contributing to the generation of immunosuppressive conditions. At the same time, IL-33 causes tumor infiltration with cytotoxic CD8 T lymphocytes and natural killers, which leads to cytolysis-mediated cancer cell death. This review describes the versatile role of the IL-33/ST2 cascade in the development of experimental and clinical tumors. In addition, we discuss the prospects for the application of IL-33 and ST2 as diagnostic biomarkers and targets for cancer immunotherapy.

摘要

白细胞介素-33(IL-33)属于IL-1细胞因子家族,作为一种危险信号发挥作用。IL-33从应激或坏死细胞中释放出来。最初,IL-33被描述为体液免疫反应的诱导剂,它激活参与调节炎症和过敏反应的Th2细胞和肥大细胞。此外,IL-33作为Th1、NK和CD8T细胞的刺激物,诱导针对细胞内病原体的细胞毒性免疫反应。最近发现,这种细胞因子通过发挥促肿瘤和抗肿瘤功能参与癌症的发展。IL-33可直接影响肿瘤细胞,促进其增殖、存活和转移。此外,IL-33通过重塑肿瘤微环境和诱导血管生成来刺激肿瘤发生,从而导致免疫抑制条件的产生。同时,IL-33导致细胞毒性CD8 T淋巴细胞和自然杀伤细胞浸润肿瘤,从而导致细胞溶解介导的癌细胞死亡。这篇综述描述了IL-33/ST2级联在实验性和临床肿瘤发展中的多方面作用。此外,我们还讨论了将IL-33和ST2作为诊断生物标志物和癌症免疫治疗靶点的应用前景。

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