非常规 T 细胞在泌尿系统肿瘤中:能抓住就抓住
Unconventional T cells in urological cancers: catch them if you can.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Characterization of Immune Infiltrating Cells in Bladder Urothelial Carcinoma and Its Clinical Significance.
Characterization of Immune Infiltrating Cells in Bladder Urothelial Carcinoma and Its Clinical Significance.
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本研究成功开发并验证了基于全面免疫细胞浸润分析的预后模型(IRPS)及其综合指数(ICPI)。IRPS/ICPI 可作为预测 BLCA 患者预后和指导免疫治疗策略的有效工具,同时也有助于识别可能从免疫治疗中获益的患者群体。
免疫细胞与肿瘤的发生和进展有关,其存在常被用于预测疾病预后。然而,就膀胱尿路上皮癌(BLCA)而言,尚未对不同类型免疫细胞的功能和预后价值进行全面研究。
我们整合了来自14个公共数据集的2300多名BLCA患者的数据。随后,我们使用ssGSEA算法分析了170种不同免疫细胞特征的数量。通过meta分析和单变量Cox分析,我们识别了与预后相关的免疫细胞,并建立了一个免疫细胞相关预后特征(IRPS)。接着,我们进行了生存分析,以观察不同IRPS风险组之间的生存差异。此外,基于与IRPS相关的DEGs,我们筛选了潜在的靶向治疗药物。最后,我们将IRPS与临床特征相结合,建立了一个综合预后指数(ICPI)。
我们的分析确定了90种与BLCA特别相关的免疫细胞类型。随后我们构建并验证了IRPS,高IRPS与更长的总生存期显著相关(HR = 0.73,95% CI,0.71-0.76,p < 0.001)。在两个独立的免疫治疗队列(IMvigor210和GSE78220)中,高IRPS的患者在接受免疫检查点抑制剂治疗后表现出显著延长的生存期(p = 0.035,p = 0.019)。确定了若干靶向IRPS的候选药物。通过将IRPS与临床特征整合而开发的ICPI,在预后分析中也表现出更高的准确性。
Immune cells have been linked to the initiation and progression of tumors, and their presence is often used to predict disease prognosis. However, when it comes to bladder urothelial carcinoma (BLCA), there has not been a comprehensive investigation into the function and prognostic value of different immune cell types.
We integrated data from more than 2300 BLCA patients across 14 public datasets. Then we analyzed the quantity of 170 different immune cell signatures using the ssGSEA algorithm. Through meta-analysis and univariable Cox analysis, we identified prognosis-associated immune cells and established an immune cell related prognostic signature (IRPS). We then conducted survival analyses to observe the differences in survival across different IRPS-risk groups. Furthermore, based on the DEGs associated with IRPS, we screened for potential targeted therapeutic agents. Finally, we integrated IRPS with clinical features to establish a comprehensive prognostic index (ICPI).
Our analysis identified 90 immune cell types that were particularly relevant to BLCA. Then we constructed and validated the IRPS, with high IRPS significantly associated with longer overall survival (HR = 0.73, 95% CI, 0.71-0.76, p < 0.001). In two independent immunotherapy cohorts (IMvigor210 and GSE78220), patients with high IRPS demonstrated significantly prolonged survival following immune checkpoint inhibitor treatment (p = 0.035, p = 0.019). Several candidate drugs targeting IRPS were identified. The ICPI, developed by integrating IRPS with clinical features, also demonstrated enhanced accuracy in prognostic analysis.
This study successfully developed and validated a prognostic signature (IRPS) based on comprehensive immune cell infiltration analysis, along with its integrated index (ICPI). IRPS/ICPI serves as an effective tool for predicting BLCA patient prognosis and guiding immunotherapy strategies, while also aiding in the identification of patient populations likely to benefit from immunotherapy.
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