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首页> 外文期刊>EBioMedicine >Tumour immune cell infiltration and survival after platinum-based chemotherapy in high-grade serous ovarian cancer subtypes: A gene expression-based computational study
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Tumour immune cell infiltration and survival after platinum-based chemotherapy in high-grade serous ovarian cancer subtypes: A gene expression-based computational study

机译:高级浆液癌亚型铂类化疗后肿瘤免疫细胞浸润和存活:基于基于基于基因的基因表达的计算研究

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Background Increasing evidence supports that the immune infiltration of tumours is associated with prognosis. Here, we sought to assess the relevance of the cellular composition of the immune infiltrate to survival after platinum-based chemotherapy amongst patients with high-grade serous ovarian cancer and evaluate these effects by molecular subtype. Methods We searched publicly available databases and identified 13 studies with more than 2000 patients. We estimated the proportions of 22 immune cell subsets by using a computational approach (CIBERSORT). Then, we investigated the associations between each immune cell subset and progression-free survival (PFS) and overall survival (OS), with cellular proportions modelled as quartiles. Findings A high fraction of M1 [hazard ratio (HR)?=?0.92, 95% confidence interval (CI)?=?0.86–0.99] and M0 (HR?=?0.93, 95% CI?=?0.87–0.99) macrophages emerged as the most closely associated with favourable OS. Neutrophils were associated with poor OS (HR?=?1.06, 95% CI?=?1.00–1.13) and PFS (HR?=?1.10, 95% CI?=?1.02–1.13). Amongst the immunoreactive tumours, the M0 macrophages and the CD8+ T cells were associated with improved OS, whereas the M2 macrophages conferred worse OS. Interestingly, PD-1 was associated with good OS (HR=0.89, 95% CI?=?0.80–1.00) and PFS (HR=0.89, 95% CI?=?0.79–1.01) in this subtype. Four subgroups of tumours with distinct survival patterns were identified using immune cell proportions with unsupervised clustering. Interpretation Further investigations of the quantitative cellular immune infiltrations in tumours may contribute to therapeutic advances.
机译:背景技术越来越多的证据支持肿瘤的免疫浸润与预后有关。在这里,我们试图评估免疫浸润的细胞组合物的相关性在高级浆液癌患者中铂的化疗后生存,并通过分子亚型评估这些影响。方法我们搜索公开的数据库,并确定了2000多名患者的13项研究。我们通过使用计算方法(Cibersort)估计了22个免疫细胞亚群的比例。然后,我们研究了每种免疫细胞子集和无进展生存(PFS)和总存活(OS)之间的关联,其具有如四分位数建模的细胞比例。发现M1的高分数[危害比(HR)吗?=Δ= 0.92,95%置信区间(CI)?= 0.86-0.99]和M0(HR?= 0.93,95%CI?= 0.87-0.99)巨噬细胞被出现为与有利的操作系统最密切相关。中性粒细胞与差的OS(HR?= 1.06,95%CI?=?1.00-1.13)和PFS(HR?=?1.10,95%CI?=?1.02-1.13)。在免疫反应性肿瘤中,M0巨噬细胞和CD8 + T细胞与改进的OS相关,而M2巨噬细胞赋予较差的OS。有趣的是,PD-1与良好的OS相关(HR = 0.89,95%CI?= 0.80-1.00)和PFS(HR = 0.89,95%CI?=?0.79-1.01)。使用免疫细胞比例与未经监督的聚类,鉴定出具有不同存活模式的四个肿瘤亚组。解释进一步调查肿瘤中定量细胞免疫浸润可能有助于治疗进展。

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