Interleukin‐35 has a tumor‐promoting role in hepatocellular carcinoma,Clinical & Experimental Immunology

当前位置： X-MOL 学术 › Clin. Exp. Immunol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Interleukin‐35 has a tumor‐promoting role in hepatocellular carcinoma
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-10-08 , DOI: 10.1111/cei.13535
X Liu ₁ , H Ren ₁ , H Guo ₁ , W Wang ₁ , N Zhao ₁

Affiliation

Hepatic inflammatory response is a risk factor for liver cancer initiation and progression. Interleukin (IL)‐35 is the newest member of the IL‐12 cytokine family, and has been reported to play an essential role in the immunosuppressive liver microenvironment. Herein we focus on the expression profiles of IL‐35 in hepatocellular carcinoma (HCC) and effects on local immune status. HCC transcriptome array data were downloaded from Gene Expression Omnibus (GEO). Analysis was performed by BRB‐Array Tools and Ingenuity Pathway Analysis (IPA) software. Serum IL‐35 level was detected by AimPlet bead‐based immunoassay. In‐situ IL‐35 detection was performed by immunohistochemical staining and Western blot. The n‐vitro effect of IL‐35 on CD4⁺ or CD8⁺ T cell function was detected by flow cytometry. Our results showed that there were large amounts of IL‐35 expressed in HCC serum and tumor tissues. IL‐35 expression affects the transcript of thousands of genes, most differentially expressed genes (DEGs), in tumor tissues correlated with T cell immunity. The IL‐35 high‐expression group exhibited enhancement of regulatory T cells (T_regs) and impairment of cytolytic T cells. In‐vitro experiments proved that exogenous IL‐35 stimulated the expression of programmed cell death 1 (PD‐1) and lymphocyte activation gene‐3 (LAG3) in CD4⁺ and CD8⁺ T cells. In addition, the stimulating effect was time‐dependent. Furthermore, IL‐35 inhibited interferon (IFN)‐γ secretion by CD4⁺ and CD8⁺ T cells. Elevated IL‐35 had an immune suppressive role in HCC tumor microenvironments through affecting inhibitor receptor expression and cytokine secretion of CD4⁺ and CD8⁺ T cells. Dissection of the precise targets and underlying molecular mechanisms would mean alternative treatments for HCC patients.

中文翻译：

白细胞介素-35在肝细胞癌中具有促肿瘤作用

肝脏炎症反应是肝癌发生和进展的危险因素。白细胞介素 (IL)-35 是 IL-12 细胞因子家族的最新成员，据报道在免疫抑制肝脏微环境中发挥重要作用。在此，我们关注肝细胞癌 (HCC) 中 IL-35 的表达谱及其对局部免疫状态的影响。HCC 转录组阵列数据从 Gene Expression Omnibus (GEO) 下载。通过 BRB-Array Tools 和 Ingenuity Pathway Analysis (IPA) 软件进行分析。通过基于 AimPlet 珠的免疫测定法检测血清 IL-35 水平。通过免疫组织化学染色和蛋白质印迹进行原位IL-35 检测。IL-35 对 CD4 ⁺或 CD8 ⁺的体外效应流式细胞仪检测T细胞功能。我们的研究结果表明，在 HCC 血清和肿瘤组织中表达了大量的 IL-35。IL-35 表达影响与 T 细胞免疫相关的肿瘤组织中数千个基因的转录，其中大多数是差异表达基因 (DEG)。IL-35 高表达组表现出调节性 T 细胞 (T _regs ) 增强和溶细胞性 T 细胞受损。体外实验证明，外源性 IL-35 刺激了 CD4 ⁺和 CD8 ⁺ T 细胞中程序性细胞死亡 1 (PD-1) 和淋巴细胞激活基因-3 (LAG3) 的表达。此外，刺激作用是时间依赖性的。^{此外，IL-35 通过 CD4 +}抑制干扰素 (IFN)-γ 的分泌。和 CD8 ⁺ T 细胞。^{升高的 IL-35 通过影响 CD4 +}和 CD8 ⁺ T 细胞的抑制剂受体表达和细胞因子分泌，在 HCC 肿瘤微环境中具有免疫抑制作用。对精确靶点和潜在分子机制的剖析将意味着 HCC 患者的替代疗法。

更新日期：2020-10-08

点击分享查看原文

点击收藏

阅读更多本刊最新论文