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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.
EBioMedicine ( IF 9.7 ) Pub Date : 2020-01-03 , DOI: 10.1016/j.ebiom.2019.102602
Rong Liu 1 , Rong Hu 2 , Ying Zeng 1 , Wei Zhang 1 , Hong-Hao Zhou 1
Affiliation  

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.

中文翻译:

铂类化学疗法治疗高级浆液性卵巢癌亚型后肿瘤免疫细胞浸润和存活:基于基因表达的计算研究。

背景技术越来越多的证据支持肿瘤的免疫浸润与预后相关。在这里,我们寻求评估铂类化疗后高级别浆液性卵巢癌患者的免疫浸润细胞组成与生存的相关性,并通过分子亚型评估这些影响。方法我们搜索了可公开获得的数据库,并确定了13项针对2000多名患者的研究。我们使用计算方法(CIBERSORT)估计了22个免疫细胞亚群的比例。然后,我们研究了每个免疫细胞亚群与无进展生存期(PFS)和总体生存期(OS)之间的关联,并将细胞比例建模为四分位数。发现M1的比例很高[风险比(HR)= 0.92,95%置信区间(CI)= 0.86-0.99]和M0(HR = 0。93、95%CI = 0.87-0.99)的巨噬细胞与良好的OS密切相关。中性粒细胞与不良OS(HR = 1.06,95%CI = 1.00-1.13)和PFS(HR = 1.10,95%CI = 1.02-1.13)相关。在免疫反应性肿瘤中,M0巨噬细胞和CD8 + T细胞与OS改善相关,而M2巨噬细胞导致OS恶化。有趣的是,在该亚型中,PD-1与良好的OS(HR = 0.89,95%CI = 0.80-1.00)和PFS(HR = 0.89,95%CI = 0.79-1.01)相关。使用无监督聚类的免疫细胞比例鉴定了具有不同生存模式的四个肿瘤亚组。解释肿瘤中定量细胞免疫浸润的进一步研究可能有助于治疗进展。99)巨噬细胞与良好的OS密切相关。中性粒细胞与不良OS(HR = 1.06,95%CI = 1.00-1.13)和PFS(HR = 1.10,95%CI = 1.02-1.13)相关。在免疫反应性肿瘤中,M0巨噬细胞和CD8 + T细胞与OS改善相关,而M2巨噬细胞导致OS恶化。有趣的是,在该亚型中,PD-1与良好的OS(HR = 0.89,95%CI = 0.80-1.00)和PFS(HR = 0.89,95%CI = 0.79-1.01)相关。使用无监督聚类的免疫细胞比例鉴定了具有不同生存模式的四个肿瘤亚组。解释肿瘤中定量细胞免疫浸润的进一步研究可能有助于治疗进展。99)巨噬细胞与良好的OS密切相关。中性粒细胞与不良OS(HR = 1.06,95%CI = 1.00-1.13)和PFS(HR = 1.10,95%CI = 1.02-1.13)相关。在免疫反应性肿瘤中,M0巨噬细胞和CD8 + T细胞与OS改善相关,而M2巨噬细胞导致OS恶化。有趣的是,在该亚型中,PD-1与良好的OS(HR = 0.89,95%CI = 0.80-1.00)和PFS(HR = 0.89,95%CI = 0.79-1.01)相关。使用无监督聚类的免疫细胞比例鉴定了具有不同生存模式的四个肿瘤亚组。解释肿瘤中定量细胞免疫浸润的进一步研究可能有助于治疗进展。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OS改善相关,而M2巨噬细胞导致OS恶化。有趣的是,在该亚型中,PD-1与良好的OS(HR = 0.89,95%CI = 0.80-1.00)和PFS(HR = 0.89,95%CI = 0.79-1.01)相关。使用无监督聚类的免疫细胞比例鉴定了具有不同生存模式的四个肿瘤亚组。解释肿瘤中定量细胞免疫浸润的进一步研究可能有助于治疗进展。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OS改善相关,而M2巨噬细胞导致OS恶化。有趣的是,在该亚型中,PD-1与良好的OS(HR = 0.89,95%CI = 0.80-1.00)和PFS(HR = 0.89,95%CI = 0.79-1.01)相关。使用无监督聚类的免疫细胞比例鉴定了具有不同生存模式的四个肿瘤亚组。解释肿瘤中定量细胞免疫浸润的进一步研究可能有助于治疗进展。95%CI = 0.79-1.01)。使用无监督聚类的免疫细胞比例鉴定了具有不同生存模式的四个肿瘤亚组。解释肿瘤中定量细胞免疫浸润的进一步研究可能有助于治疗进展。95%CI = 0.79-1.01)。使用无监督聚类的免疫细胞比例鉴定了具有不同生存模式的四个肿瘤亚组。解释肿瘤中定量细胞免疫浸润的进一步研究可能有助于治疗进展。
更新日期:2020-01-04
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