在多种癌症中，白细胞介素18受体辅助蛋白（IL18RAP）表达异常，这种异常与肿瘤免疫和异质性临床结局相关。本研究通过生物信息学分析发现，IL18RAP与人类肿瘤微环境相关，并促进不同的免疫细胞浸润。此外，多重免疫荧光染色显示，IL18RAP表达增加时，浸润的M1巨噬细胞数量增加。通过使用IL18RAP敲除的三种人类癌细胞系（MDA-MB-231，U251和HepG2）进行共培养迁移分析，证实了这一发现。我们通过Spearman相关分析发现，IL18RAP与大部分免疫刺激剂、免疫抑制剂、主要组织相容性复合物（MHC）分子、趋化因子和趋化因子受体基因存在正相关关系。此外，功能性IL18RAP的基因集富集分析（GSEA）显示，它与多种免疫过程相关，如干扰素γ产生的正调节和NK细胞介导免疫的正调节。此外，我们使用单细胞RNA测序分析检测到IL18RAP主要表达在免疫细胞中，并通过HALLMARK分析证实INF-γ基因集表达在CD8Tex细胞中上调。另外，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的反应。总之，我们的研究表明IL18RAP是一种新的肿瘤生物标志物，可能成为癌症免疫治疗的潜在靶点。

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.