Division of Hematology, Department of Internal Medicine, Karolinska Institutet, Stockholm, Sweden.
Clin Cancer Res. 2010 Jan 15;16(2):637-50. doi: 10.1158/1078-0432.CCR-09-2487. Epub 2010 Jan 12.
The microenvironment influences outcome in follicular lymphoma. Our hypothesis was that several immune cell subsets are important for disease outcome and their individual prognostic importance should be demonstrable in the same analysis and in competition with clinical factors.
Seventy follicular lymphoma patients with extreme clinical outcome ("poor" and "good" cases) were selected in a population-based cohort of 197. None of the 37 good-outcome patients died from lymphoma, whereas all the 33 poor-outcome patients succumbed in <or=5 years. Furthermore, the good-outcome patients were followed for a long time and needed no or little treatment. A tissue microarray was constructed from diagnostic, pretreatment biopsies. Cellular subsets were quantified after immunostaining, using computerized image analysis, separating cells inside and outside the follicles (follicular and interfollicular compartments). Flow cytometry data from the same samples were also used.
Independently of the Follicular Lymphoma International Prognostic Index, CD4(+) cells were associated with poor outcome and programmed death-1-positive and CD8(+) cells were associated with good outcome. The prognostic values of CD4(+) and programmed death-1-positive cells were accentuated when they were follicular and that of CD8(+) cells were accentuated when they were interfollicular. Follicular FOXP3(+) cells were associated with good outcome and interfollicular CD68(+) cells were associated with poor outcome. Additionally, high CD4/CD8 and CD4 follicular/interfollicular ratios correlated with poor outcome.
There are many important immune cell subsets in the microenvironment of follicular lymphoma. Each of these is independently associated with outcome. This is the first study showing the effect of the balance of the entire microenvironment, not only of individual subsets.
滤泡性淋巴瘤的微环境会影响预后。我们的假设是，几种免疫细胞亚群对疾病的预后很重要，并且它们各自的预后意义应该能够在同一分析中以及与临床因素的竞争中得到证明。
在一个基于人群的 197 例队列中，选择了 70 例滤泡性淋巴瘤患者，这些患者具有极端的临床结局（“不良”和“良好”病例）。37 例预后良好的患者中没有一人因淋巴瘤而死亡，而 33 例预后不良的患者在 5 年内全部死亡。此外，这些预后良好的患者随访时间长，无需或只需少量治疗。从诊断前活检构建组织微阵列。使用计算机图像分析对免疫染色后的细胞亚群进行定量，将细胞分为滤泡内和滤泡外（滤泡和滤泡间区室）。还使用了来自相同样本的流式细胞术数据。
独立于滤泡性淋巴瘤国际预后指数，CD4+细胞与不良预后相关，程序性死亡受体-1阳性和 CD8+细胞与良好预后相关。当 CD4+和程序性死亡受体-1 阳性细胞位于滤泡内时，其预后价值会被放大，而当 CD8+细胞位于滤泡间区时，其预后价值会被放大。滤泡内 FOXP3+细胞与良好预后相关，滤泡间 CD68+细胞与不良预后相关。此外，高 CD4/CD8 和 CD4 滤泡内/滤泡间比值与不良预后相关。
滤泡性淋巴瘤的微环境中有许多重要的免疫细胞亚群。这些亚群中的每一个都与预后独立相关。这是第一项显示整个微环境平衡而非单个亚群的影响的研究。
