Chee Serena J, Lopez Maria, Mellows Toby, Gankande Sharmali, Moutasim Karwan A, Harris Scott, Clarke James, Vijayanand Pandurangan, Thomas Gareth J, Ottensmeier Christian H
Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK.
NIHR Southampton Biomedical Research Centre, Tremona Road Southampton General Hospital Southampton SO16 6YD, UK.
Br J Cancer. 2017 Oct 24;117(9):1341-1348. doi: 10.1038/bjc.2017.269. Epub 2017 Aug 17.
We systematically assessed the prognostic and predictive value of infiltrating adaptive and innate immune cells in a large cohort of patients with advanced mesothelioma.
A tissue microarray from 302 samples was constructed. Markers of adaptive immune response in T-cells (CD8, FOXP3, CD4, CD45RO, CD3) and B-cells (CD20), and of innate immune response; neutrophils (NP57), natural killer cells (CD56) and macrophages (CD68) were evaluated.
We found that in the epithelioid tumours, high CD4 and CD20 counts, and low FOXP3, CD68 and NP57 counts linked to better outcome. In the non-epithelioid group low CD8 and low FOXP3 counts were beneficial.On multivariate analysis low FOXP3 remained independently associated with survival in both groups. In the epithelioid group additionally high CD4, high CD20, and low NP57 counts were prognostic.
Our data demonstrate for the first time, in predominately advanced disease, the association of key markers of adaptive and innate immunity with survival and the differential effect of histology. A better understanding of the immunological drivers of the different subtypes of mesothelioma will assist prognostication and disease-specific clinical decision-making.
我们系统评估了晚期间皮瘤患者队列中浸润性适应性和先天性免疫细胞的预后和预测价值。
构建了一个包含302个样本的组织微阵列。评估了T细胞(CD8、FOXP3、CD4、CD45RO、CD3)和B细胞(CD20)中适应性免疫反应的标志物,以及先天性免疫反应的标志物;中性粒细胞(NP57)、自然杀伤细胞(CD56)和巨噬细胞(CD68)。
我们发现,在上皮样肿瘤中,高CD4和CD20计数以及低FOXP3、CD68和NP57计数与更好的预后相关。在非上皮样组中,低CD8和低FOXP3计数是有益的。多因素分析显示,低FOXP3在两组中均与生存独立相关。在上皮样组中,高CD4、高CD20和低NP57计数也具有预后意义。
我们的数据首次表明,在主要为晚期疾病的情况下,适应性和先天性免疫的关键标志物与生存之间存在关联,且组织学有不同影响。更好地了解间皮瘤不同亚型的免疫驱动因素将有助于预后评估和疾病特异性临床决策。