IL18RAP 在人类癌症中的预后和免疫作用。
Prognostic and immunological roles of IL18RAP in human cancers.
机构信息
Department of Urology, Hubei International Scientific and Technological Cooperation Base of Immunotherapy, Renmin Hospital of Wuhan University, Wuhan 430000, Hubei, P.R. China.
出版信息
Aging (Albany NY). 2023 Sep 11;15(17):9059-9085. doi: 10.18632/aging.205017.
Across several cancers, IL18 receptor accessory protein (IL18RAP) is abnormally expressed, and this abnormality is related to tumor immunity and heterogeneous clinical outcomes. In this study, based on bioinformatics analysis, we discovered that IL18RAP is related to the human tumor microenvironment and promotes various immune cells infiltration. Additionally, the multiple immunofluorescence staining revealed that with the increased expression of IL18RAP, the number of infiltrated M1 macrophages increased. This finding was confirmed by coculture migration analysis using three human cancer cell lines (MDA-MB-231, U251, and HepG2) with IL18RAP knockdown. We discovered a positive link between IL18RAP and the majority of immunostimulators, immunoinhibitors, major histocompatibility complex (MHC) molecules, chemokines, and chemokine receptor genes using Spearman correlation analysis. Additionally, functional IL18RAP's gene set enrichment analysis (GSEA) revealed that it is related to a variety of immunological processes, such as positive regulation of interferon gamma production and positive regulation of NK cell-mediated immunity. Moreover, we used single-cell RNA sequencing analysis to detect that IL18RAP was mainly expressed in immune cells, and HALLMARK analysis confirmed that the INF-γ gene set expression was upregulated in CD8Tex cells. In addition, in human and mouse cancer cohorts, we found that the level of IL18RAP can predict the immunotherapy response. In short, our study showed that IL18RAP is a new tumor biomarker and may become a potential immunotherapeutic target in cancer.
在多种癌症中,白细胞介素 18 受体辅助蛋白(IL18RAP)异常表达,这种异常与肿瘤免疫和异质性临床结局有关。在这项研究中,我们基于生物信息学分析发现,IL18RAP 与人类肿瘤微环境有关,并促进各种免疫细胞浸润。此外,多重免疫荧光染色显示,随着 IL18RAP 表达的增加,浸润的 M1 巨噬细胞数量增加。这一发现通过使用三种人类癌细胞系(MDA-MB-231、U251 和 HepG2)进行 IL18RAP 敲低的共培养迁移分析得到了证实。我们使用 Spearman 相关性分析发现,IL18RAP 与大多数免疫刺激剂、免疫抑制剂、主要组织相容性复合体(MHC)分子、趋化因子和趋化因子受体基因之间存在正相关。此外,功能性 IL18RAP 的基因集富集分析(GSEA)表明,它与多种免疫过程有关,如干扰素γ产生的正向调节和 NK 细胞介导的免疫的正向调节。此外,我们使用单细胞 RNA 测序分析检测到 IL18RAP 主要在免疫细胞中表达,并且 HALLMARK 分析证实 CD8Tex 细胞中 INF-γ 基因集的表达上调。此外,在人类和小鼠癌症队列中,我们发现 IL18RAP 的水平可以预测免疫治疗反应。总之,我们的研究表明,IL18RAP 是一种新的肿瘤标志物,可能成为癌症免疫治疗的潜在靶点。