Alvaro Tomás, Lejeune Marylène, Salvadó Ma Teresa, Bosch Ramón, García Juan F, Jaén Joaquín, Banham Alison H, Roncador Giovanna, Montalbán Carlos, Piris Miguel A
Department of Pathology, Hospital Verge de la Cinta, C/Esplanetes n degree 14, 43500-Tortosa, Spain.
Clin Cancer Res. 2005 Feb 15;11(4):1467-73. doi: 10.1158/1078-0432.CCR-04-1869.
Recent studies of Hodgkin's lymphoma (HL) have suggested that the presence of regulatory T cells in the reactive background may explain the inhibition of the antitumoral host immune response observed in these patients. This study aimed to assess the relevance of regulatory T cells and CTLs present in the background of HL samples in the prognosis of a series of classic HL (cHL) patients.
Expression of granzyme B and TIA-1 (markers for CTL) and FOXP3 (a marker for regulatory T cells) were evaluated independently by immunohistochemistry in tissue microarrays of 257 cHL patients and correlated with patient outcome.
The combined influence of the presence of FOXP3(+) and TIA-1(+) cells distinguished three risk groups of patients with 5-year overall survival of 100%, 88%, and 73%. The presence of a small number of FOXP3(+) cells and a high proportion of TIA-1(+) cells in the infiltrate represent an independent prognostic factor that negatively influenced event-free survival and disease-free survival in cHL. Compared with the features at diagnosis, relapsed samples tended to have more TIA-1(+) cells and a lower proportion of FOXP3(+) cells in the reactive background.
These data suggest that low infiltration of FOXP3(+) cells in conjunction with high infiltration of TIA-1(+) cells in cHL may represent biological markers predicting an unfavorable outcome. Moreover, the variation of these markers over the course of the disease implies a possible role for them in the progression of HL cases.
近期对霍奇金淋巴瘤(HL)的研究表明,反应性背景中调节性T细胞的存在可能解释了在这些患者中观察到的抗肿瘤宿主免疫反应的抑制。本研究旨在评估HL样本背景中存在的调节性T细胞和细胞毒性T淋巴细胞(CTL)与一系列经典型HL(cHL)患者预后的相关性。
通过免疫组织化学在257例cHL患者的组织微阵列中独立评估颗粒酶B和TIA-1(CTL标志物)以及FOXP3(调节性T细胞标志物)的表达,并将其与患者预后相关联。
FOXP3(+)和TIA-1(+)细胞存在的综合影响区分出三组风险患者,其5年总生存率分别为100%、88%和73%。浸润中少量FOXP3(+)细胞和高比例TIA-1(+)细胞的存在是一个独立的预后因素,对cHL患者的无事件生存期和无病生存期产生负面影响。与诊断时的特征相比,复发样本在反应性背景中往往有更多的TIA-1(+)细胞和更低比例的FOXP3(+)细胞。
这些数据表明,cHL中FOXP3(+)细胞低浸润与TIA-1(+)细胞高浸润可能代表预测不良预后的生物学标志物。此外,这些标志物在疾病过程中的变化意味着它们在HL病例进展中可能发挥作用。