Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma
Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma
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DOI：
10.3324/haematol.11702
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发表时间：
2008-01-31
期刊：
影响因子：
10.1
通讯作者：
Dirnhofer, Stephan
中科院分区：
文献类型：
--
作者：
Tzankov, Alexandar;Meier, Cecile;Dirnhofer, Stephan
肿瘤微环境是影响肿瘤行为的重要因素。我们评估了FOXP3（+）调节性t细胞（Treg）在淋巴瘤中的分布及其生物学意义。设计与方法采用免疫组织化学方法对1019例不同类型淋巴瘤的肿瘤内FOXP3（+）细胞的绝对数量进行了研究，并在单因素和多因素模型中与表型和临床参数进行了相关性研究。采用受试者工作特征曲线确定FOXP3（+）细胞密度的预后临界值。结果1019例患者中，926例（91%）可评价。FOXP3（+）细胞密度在不同的淋巴瘤实体之间存在差异，滤泡性淋巴瘤中FOXP3（+）细胞密度最高。肿瘤浸润的FOXP3（+）细胞数量超过受体工作特征确定的临界值，对滤泡性淋巴瘤的疾病特异性和无失败生存（p=0.053）、生发中心样弥漫性大b细胞淋巴瘤的疾病特异性生存（p=0.051）以及经典霍奇金淋巴瘤的总体和无失败生存（p= 0.004）均有积极影响，但对非生发中心弥漫性大b细胞淋巴瘤的预后有负面影响（p=0.059）。在Cox回归模型中，考虑分期和年龄，FOXP3（+）细胞的数量对于经典霍奇金淋巴瘤的无衰竭生存具有独立的预后意义，对于经典霍奇金淋巴瘤的总生存以及生发中心样和非生发中心弥漫性大b细胞淋巴瘤的疾病特异性生存具有临界意义。结论foxp3（+）细胞是重要的淋巴瘤/宿主微环境调节剂。评估FOXP3（+）细胞密度有助于预测弥漫性大b细胞淋巴瘤、淋巴性淋巴瘤和经典霍奇金淋巴瘤的预后。
BackgroundThe tumor microenvironment is important for the behavior of cancer. We assessed the distribution and biological significance of FOXP3(+) regulatory T-cells (Treg) in lymphomas.Design and MethodsThe absolute number of intratumoral FOXP3(+) cells was immunohistochemically studied on lymphoma tissue microarrays from 1019 cases of different types of lymphomas and correlated to phenotypic and clinical parameters in uni- and multivariate models. Receiver operating characteristic curves were used to determine prognostic cut-off values of FOXP3(+) cell density.ResultsOf the 1019 cases, 926 (91%) were evaluable. FOXP3(+) cell density varied between the lymphoma entities, and was highest in follicular lymphoma. An increased number of tumor-infiltrating FOXP3(+) cells over the receiver operating characteristic-determined cut-offs positively influenced both disease-specific and failure-free survival in follicular lymphoma (p=0.053) and disease-specific survival in germinal center-like diffuse large B-cell lymphoma (p=0.051) and overall and failure-free survival in classical Hodgkin's lymphoma (p-0.004), but had a negative prognostic effect in non-germinal center diffuse large B-cell lymphoma (p=0.059). In a Cox regression model, considering stage and age, the amount of FOXP3(+) cells was of independent prognostic significance for failure-free survival in classical Hodgkin's lymphoma and of borderline significance for overall survival in classical Hodgkin's lymphoma and disease-specific survival in germinal center-like and non-germinal center diffuse large B-cell lymphoma.ConclusionsFOXP3(+) cells represent important lymphoma/host microenvironment modulators. Assessment of FOXP3(+) cell density can contribute to the prediction of outcome in diffuse large B-cell lymphoma, fallicular lymphoma and classical Hodgkin's lymphoma.