Pathology and Laboratory Medicine, BC Cancer Agency Center for Lymphoid Cancers, Vancouver, BC, Canada.
Blood. 2010 Jan 14;115(2):289-95. doi: 10.1182/blood-2009-07-235598. Epub 2009 Nov 9.
Previous studies of follicular lymphoma (FL) patients treated heterogeneously have suggested that decreased numbers of regulatory T cells correlates with improved survival. We studied advanced-stage FL patients from a single institution phase 2 trial. All patients were treated uniformly with multiagent chemotherapy and radiation. Tissue microarrays were constructed using diagnostic biopsies available in 105 patients and stained with CD4, CD8, CD25, and forkhead/winged helix transcription factor 3 (FOXP3) antibodies. Both cell content and cell distribution were evaluated. For all antibodies, there were cases with a predominant intrafollicular or perifollicular localization of cells (follicular pattern) while others displayed a diffuse pattern. The median follow-up of living patients was 17.1 years. The International Prognostic Index score predicted overall survival (OS; P = .004) but not risk of transformation (RT). Cell content did not impact survival, while immunoarchitectural patterns of CD4/CD8 were significant for progression-free survival (PFS; P = .056), CD25 for both PFS and OS (P = .002 and P = .024, respectively), and FOXP3(+) predicted PFS, OS, and RT (P = .001, P < .001 and p = .002, respectively). A Cox multivariate model showed both International Prognostic Index score and FOXP3(+) pattern were independent predictors of OS (P = .008 and P < .001, respectively), while only FOXP3(+) pattern predicted RT (P = .004). We conclude that FOXP3(+) cell distribution significantly predicts survival and RT in FL.
先前对接受不同治疗方案的滤泡性淋巴瘤 (FL) 患者的研究表明，调节性 T 细胞数量减少与生存改善相关。我们研究了来自单一机构的 2 期临床试验的晚期 FL 患者。所有患者均接受多药化疗和放疗的统一治疗。使用 105 例患者的诊断性活检构建组织微阵列，并使用 CD4、CD8、CD25 和叉头/翼状螺旋转录因子 3（FOXP3）抗体进行染色。评估了细胞含量和细胞分布。对于所有抗体，有一些病例的细胞主要定位于滤泡内或滤泡周围（滤泡模式），而另一些病例则表现为弥漫模式。存活患者的中位随访时间为 17.1 年。国际预后指数评分预测了总生存（OS；P =.004），但未预测转化风险（RT）。细胞含量对生存没有影响，而 CD4/CD8 的免疫组织学模式对无进展生存期（PFS；P =.056）、CD25 对 PFS 和 OS 均有影响（P =.002 和 P =.024），FOXP3(+)预测 PFS、OS 和 RT（P =.001、P <.001 和 P =.002）。Cox 多变量模型显示，国际预后指数评分和 FOXP3(+)模式均为 OS 的独立预测因素（P =.008 和 P <.001），而 FOXP3(+)模式仅为 RT 的独立预测因素（P =.004）。我们得出结论，FOXP3(+)细胞分布显著预测 FL 的生存和 RT。
