Carreras Joaquim, Lopez-Guillermo Armando, Roncador Giovanna, Villamor Neus, Colomo Lluis, Martinez Antonio, Hamoudi Rifat, Howat William J, Montserrat Emili, Campo Elias
Hematopathology Section, Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona, Spain.
J Clin Oncol. 2009 Mar 20;27(9):1470-6. doi: 10.1200/JCO.2008.18.0513. Epub 2009 Feb 17.
Tumor microenvironment influences the behavior of follicular lymphoma (FL), although the specific cell subsets involved are not well known. The aim of this study was to determine the impact of programmed cell death 1 (PD-1) -positive inhibitory immunoregulatory lymphoid cells in the clinicobiologic features and outcome of patients with FL.
We examined samples from 100 patients (53 men and 47 women; median age, 54 years) at diagnosis, as well as in 32 patients at first relapse, with a recently generated monoclonal antibody against PD-1. The cells were quantified using computerized image analysis. Additional analysis consisted of double immunofluorescence and flow cytometry.
PD-1 expression was alternative to FOXP3 in lymphoid cells from both reactive tonsils and FL. At diagnosis, the median percentage of PD-1-positive cells was 14% (range, 0.1% to 74%). Patients with grade 3 FL, poor performance status, and high serum lactate dehydrogenase showed lower numbers of PD-1-positive cells. After a median follow-up of 6.2 years, patients with PD-1-positive cells <or= 5% (n = 25), 6% to 33% (n = 50), and more than 33% (n = 25) had a 5-year progression-free survival rate of 20%, 46%, and 48% (P = .038) and overall survival (OS) of 50%, 77%, and 95% (P = .004), respectively. PD-1 and FL International Prognostic Index maintained prognostic value for OS in multivariate analysis. Patients with PD-1-positive cells <or= 5% showed a higher risk of histologic transformation. At that time, transformed diffuse large B-cell lymphomas had lower percentage of PD-1-positive cells than FL.
A high content of PD-1-positive cells predicted favorable outcome of FL patients, whereas a marked reduction is observed in transformation.
肿瘤微环境影响滤泡性淋巴瘤（FL）的行为，尽管其中涉及的特定细胞亚群尚不清楚。本研究的目的是确定程序性细胞死亡1（PD-1）阳性抑制性免疫调节淋巴细胞对FL患者临床生物学特征和预后的影响。
我们使用一种新产生的抗PD-1单克隆抗体，检测了100例初诊患者（53例男性和47例女性；中位年龄54岁）以及32例首次复发患者的样本。使用计算机图像分析对细胞进行定量。额外的分析包括双重免疫荧光和流式细胞术。
在反应性扁桃体和FL的淋巴细胞中，PD-1表达与FOXP3表达相互替代。初诊时，PD-1阳性细胞的中位百分比为14%（范围为0.1%至74%）。3级FL、体能状态差和血清乳酸脱氢酶水平高的患者，其PD-1阳性细胞数量较少。中位随访6.2年后，PD-1阳性细胞≤5%（n = 25）、6%至33%（n = 50）和超过33%（n = 25）的患者，5年无进展生存率分别为20%、46%和48%（P = 0.038），总生存率（OS）分别为50%、77%和95%（P = 0.004）。在多变量分析中，PD-1和FL国际预后指数对OS仍具有预后价值。PD-1阳性细胞≤5%的患者发生组织学转化的风险更高。此时转化的弥漫性大B细胞淋巴瘤的PD-1阳性细胞百分比低于FL。
高含量的PD-1阳性细胞预示着FL患者预后良好，而在转化过程中则观察到明显减少。
