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ILC2 衍生的 IL-9 通过激活 CD8 T 细胞抑制结直肠癌进展。

ILC2-derived IL-9 inhibits colorectal cancer progression by activating CD8 T cells.

机构信息

The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China; Department of Immunology, Jiangsu University, Zhenjiang, 212013, China.

The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China.

出版信息

Cancer Lett. 2021 Apr 1;502:34-43. doi: 10.1016/j.canlet.2021.01.002. Epub 2021 Jan 9.

DOI:10.1016/j.canlet.2021.01.002
PMID:33429004
Abstract

Group 2 innate lymphoid cells (ILC2s), characterized by secretion of type 2 cytokines, regulate multiple immune responses. ILC2s are found in different tumor tissues, and ILC2-derived interleukin (IL)-4, IL-5, and IL-13 act on the cells in tumor microenvironment to participate in tumor progression. ILC2s are abundant in colorectal cancer (CRC) tissue, but the role of ILC2s in CRC remains unclear. In this study, we found that the percentage of ILC2s was higher in CRC tissue than in the adjacent normal tissue and that these ILC2s were the dominant IL-9-secreting cell-subsets in CRC tissue, as shown by flow cytometry analysis. ILC2s-derived IL-9 could activate CD8 T cells to inhibit tumor growth, while anti-IL-9 reversed this effect. In vivo experiments showed that neutralizing ILC2s promoted tumor growth, while tumor inhibition occurred by intravenous injection of IL-9. In conclusion, our results demonstrated that ILC2-derived IL-9 could activate CD8 T cells to promote anti-tumor effects in CRC.

摘要

2 型固有淋巴细胞(ILC2s)的特征是分泌 2 型细胞因子,调节多种免疫反应。ILC2s 存在于不同的肿瘤组织中,ILC2 衍生的白细胞介素(IL)-4、IL-5 和 IL-13 作用于肿瘤微环境中的细胞,参与肿瘤的进展。ILC2s 在结直肠癌(CRC)组织中丰富,但 ILC2s 在 CRC 中的作用尚不清楚。在这项研究中,我们发现 CRC 组织中 ILC2s 的比例高于相邻正常组织,并且这些 ILC2s 是 CRC 组织中占主导地位的 IL-9 分泌细胞亚群,这通过流式细胞术分析得到证实。ILC2s 衍生的 IL-9 可以激活 CD8 T 细胞抑制肿瘤生长,而抗 IL-9 逆转了这种作用。体内实验表明,中和 ILC2s 促进肿瘤生长,而静脉注射 IL-9 则抑制肿瘤。总之,我们的结果表明,ILC2 衍生的 IL-9 可以激活 CD8 T 细胞,促进 CRC 的抗肿瘤作用。

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