Apte Ron N, Krelin Yakov, Song Xiaoping, Dotan Shahar, Recih Eli, Elkabets Moshe, Carmi Yaron, Dvorkin Tatyana, White Roslayn M, Gayvoronsky Lubov, Segal Shraga, Voronov Elena
Department of Microbiology and Immunology and Faculty of Health Sciences and The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Eur J Cancer. 2006 Apr;42(6):751-9. doi: 10.1016/j.ejca.2006.01.010. Epub 2006 Mar 10.
Interleukin-1 (IL-1) comprises a family of closely related genes; the two major agonistic proteins, IL-1alpha and IL-1beta, are pleiotropic and affect mainly inflammation, immunity and haemopoiesis. IL-1beta is active solely in its secreted form, whereas IL-1alpha is active mainly as an intracellular precursor. IL-1 is abundant at tumour sites, where it may affect the process of carcinogenesis, tumour growth and invasiveness and the patterns of tumour-host interactions. Here, we review the effects of micro-environment- and tumour cell-derived IL-1 on malignant processes in experimental tumour models. We propose that membrane-associated IL-1alpha expressed on malignant cells stimulates anti-tumour immunity, while secretable IL-1beta derived from the micro-environment or the malignant cells, activates inflammation that promotes invasiveness and induces tumour-mediated suppression. Inhibition of the function of IL-1 by the inhibitor of IL-1, interleukin-1 receptor antagonist (IL-1Ra), reduces tumour invasiveness and alleviates tumour-mediated suppression, pointing to its feasible use in cancer therapy. Differential manipulation of IL-1alpha and IL-1beta in malignant cells or in the tumour's micro-environment may open new possibilities for using IL-1 in cancer immunotherapy.
白细胞介素-1（IL-1）由一组密切相关的基因组成；两种主要的激动蛋白，即IL-1α和IL-1β，具有多效性，主要影响炎症、免疫和造血过程。IL-1β仅以其分泌形式具有活性，而IL-1α主要作为细胞内前体具有活性。IL-1在肿瘤部位大量存在，在那里它可能影响致癌过程、肿瘤生长和侵袭以及肿瘤与宿主的相互作用模式。在此，我们综述了微环境和肿瘤细胞来源的IL-1对实验性肿瘤模型中恶性过程的影响。我们提出，恶性细胞上表达的膜相关IL-1α刺激抗肿瘤免疫，而来自微环境或恶性细胞的可分泌IL-1β激活促进侵袭并诱导肿瘤介导的抑制的炎症。通过IL-1抑制剂白细胞介素-1受体拮抗剂（IL-1Ra）抑制IL-1的功能，可降低肿瘤侵袭性并减轻肿瘤介导的抑制，表明其在癌症治疗中的可行用途。对恶性细胞或肿瘤微环境中IL-1α和IL-1β的差异调控可能为在癌症免疫治疗中使用IL-1开辟新的可能性。
