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白细胞介素21在小鼠模型中的治疗作为结肠癌一种新型潜在的细胞因子免疫疗法。

Interleukin 21 treatment in a murine model as a novel potential cytokine immunotherapy for colon cancer.

作者信息

Chen Chen, Liu Xiaoning, Ren Yi

机构信息

Clinical School, Hubei University of Chinese Medicine, China.

Central Laboratory of Huai'an First People's Hospital, Nanjing Medical University, China.

出版信息

Adv Clin Exp Med. 2018 May;27(5):583-589. doi: 10.17219/acem/68703.

Abstract

BACKGROUND

Interleukin 21 (IL-21), which belongs to the common γ-chain (γc) family, is a novel tumor suppressor that has been shown to affect T-cell proliferation, survival and function. However, the role of IL-21 in colon cancer remains unclear.

OBJECTIVES

We sought to determine whether IL-21 could inhibit the progression of colon cancer in mice; we also explored the mechanisms underlying the immunological effects of IL-21 in colon cancer.

MATERIAL AND METHODS

Exogenous IL-21 protein was expressed to treat tumor-bearing mice and the production of cytokine interleukin 4, interferon gamma and lambda from CD4+ T, CD8+ T, and NK cells were measured, along with the survival times of these tumor-bearing mice.

RESULTS

Interleukin 21 promoted the secretion of interferon gamma from the CD4+ T, CD8+ T and NK cells and it enhanced the production of interferon lambda by the NK cells. More importantly, IL-21 treatment significantly enhanced antitumor effects in favor of tumor eradication. We also found that CD8+ T and NK cells are necessary for the antitumor immune responses elicited by IL-21.

CONCLUSIONS

Interleukin 21 is a powerful tool for activating CD8+ T cells and NK cells which exhibit potent cytolytic effector functions and should therefore be exploited for anticancer immunotherapy. Our findings support the development of a novel cytokine immunotherapy against colon cancer.

摘要

背景

白细胞介素21(IL-21)属于共同γ链(γc)家族,是一种新型肿瘤抑制因子,已被证明可影响T细胞增殖、存活和功能。然而,IL-21在结肠癌中的作用仍不清楚。

目的

我们试图确定IL-21是否能抑制小鼠结肠癌的进展;我们还探讨了IL-21在结肠癌中免疫效应的潜在机制。

材料与方法

表达外源性IL-21蛋白以治疗荷瘤小鼠,并检测CD4+T、CD8+T和NK细胞产生细胞因子白细胞介素4、干扰素γ和λ的情况,以及这些荷瘤小鼠的存活时间。

结果

白细胞介素21促进CD4+T、CD8+T和NK细胞分泌干扰素γ,并增强NK细胞产生干扰素λ。更重要的是,IL-21治疗显著增强了抗肿瘤作用,有利于肿瘤根除。我们还发现CD8+T和NK细胞对于IL-21引发的抗肿瘤免疫反应是必需的。

结论

白细胞介素21是激活具有强大细胞溶解效应功能的CD8+T细胞和NK细胞的有力工具,因此应用于抗癌免疫治疗。我们的研究结果支持开发一种针对结肠癌的新型细胞因子免疫疗法。

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