Department of Tumour Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu, China.
J Transl Med. 2020 Dec 11;18(1):477. doi: 10.1186/s12967-020-02661-w.
Interleukin-33 (IL-33) is an effective inducer of pro-inflammatory cytokines regulating innate and adaptive immunity. Inflammation could be a double-edged sword, promoting or inhibiting tumour growth. To date, the roles and mechanisms of IL-33 in tumours remain controversial. Here, we examined the effect of exogenous IL-33 on the biological characteristics of hepatocellular carcinoma (HCC) and the possible mechanism of action.
In this study, IL-33 expression in the tissues of 69 HCC patients was detected and its relationship with prognosis was evaluated. After establishing a mouse HCC model and IL-33 treatment operation, the infiltration of splenic myeloid-derived suppressor (MDSCs), dendritic (DCs), regulatory T, and natural killer (NK) cells was detected by flow cytometry analysis, and the vascular density of the tumour tissues was detected by immunohistochemistry to reveal the mechanism of IL-33 in HCC proliferation. Finally, the Cancer Genome Atlas database was used to analyse Gene Ontology terms the and Kyoto Encyclopaedia of Genes and Genomes pathway. Moreover, the chi-square test, two-tailed unpaired Student's t-test, and multiple t-tests were performed using SPSS version 23.0 and GraphPad Prism 8.0 software.
The IL-33 expression level was negatively correlated with the overall survival of HCC patients, suggesting its potential clinical significance in the prognosis of HCC. We found that systemic IL-33 administration significantly promoted the tumour size in vivo. Furthermore, the IL-33-treated mice presented decreased frequencies of tumouricidal NK and CD69 CD8 T cells. After IL-33 treatment, the incidence of monocytic MDSCs and conventional DCs increased, while that of granulocytic MDSCs decreased. Moreover, IL-33 promoted the formation of intracellular neovascularization. Therefore, IL-33 accelerated HCC progression by increasing the accumulation of immunosuppressive cells and neovascularization formation. Finally, we found that the transcription of IL-33 was closely related to the PI3K-Akt and MAPK pathways in Gene Set Enrichment Analysis plots, which were involved in the tumourigenesis and pathogenesis of HCC.
Taken together, IL-33 may be a key tumour promoter of HCC proliferation and tumourigenicity, an important mediator, and a potential therapeutic target for regulating HCC progression.
白细胞介素 33（IL-33）是一种有效的促炎细胞因子诱导物，可调节先天和适应性免疫。炎症可能是一把双刃剑，既能促进也能抑制肿瘤生长。迄今为止，IL-33 在肿瘤中的作用和机制仍存在争议。在这里，我们研究了外源性 IL-33 对肝细胞癌（HCC）生物学特性的影响及其可能的作用机制。
本研究检测了 69 例 HCC 患者组织中 IL-33 的表达，并评估了其与预后的关系。建立了小鼠 HCC 模型和 IL-33 治疗操作后，通过流式细胞术分析检测脾髓源性抑制细胞（MDSCs）、树突状细胞（DCs）、调节性 T 细胞和自然杀伤（NK）细胞的浸润情况，免疫组织化学法检测肿瘤组织的血管密度，揭示 IL-33 在 HCC 增殖中的作用机制。最后，使用癌症基因组图谱数据库分析基因本体论术语和京都基因与基因组百科全书通路。此外，使用 SPSS 版本 23.0 和 GraphPad Prism 8.0 软件进行卡方检验、双尾无配对 Student's t 检验和多重 t 检验。
IL-33 的表达水平与 HCC 患者的总生存率呈负相关，提示其在 HCC 预后中的潜在临床意义。我们发现，全身给予 IL-33 可显著促进体内肿瘤大小。此外，IL-33 处理的小鼠肿瘤杀伤性 NK 和 CD69+CD8+T 细胞频率降低。IL-33 处理后，单核来源的 MDSCs 和常规 DCs 的发生率增加，而粒细胞来源的 MDSCs 减少。此外，IL-33 促进了细胞内新生血管的形成。因此，IL-33 通过增加免疫抑制细胞的积累和新生血管形成加速了 HCC 的进展。最后，我们发现基因集富集分析图谱中 IL-33 的转录与 PI3K-Akt 和 MAPK 通路密切相关，这些通路参与了 HCC 的发生和发病机制。
综上所述，IL-33 可能是 HCC 增殖和致瘤性的关键肿瘤促进剂，是调节 HCC 进展的重要介质和潜在治疗靶点。
Zotero 插件
