文章：

PD-1表达定义了滤泡性淋巴瘤中两个不同的T细胞亚群，它们对患者生存的影响不同

PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival

原文发布日期：2015-02-20

DOI: 10.1038/bcj.2015.1

类型: Original Article

开放获取: 是

英文摘要：

To determine the biological and clinical relevance of programmed death 1 (PD-1) in follicular lymphoma (FL), we characterized PD-1+ T-cell subsets and assessed their biological function as well as potential clinical impact. We found that PD-1 is expressed on intratumoral CD4+ T cells with both bright and dim intensity, representing two different sub-populations of cells. By immunohistochemistry, we found that CD4+PD-1high T cells predominantly reside in the lymph node follicles, while PD-1low T cells are mainly located in an interfollicular pattern. Intratumoral CD4+PD-1high T cells have a TFH cell phenotype, express CXCR5, secrete IL-21 and are BCL-6 positive with no TIM-3 expression. In contrast, CD4+PD-1low T cells have an exhausted phenotype, express TIM-3 and do not express BCL-6 and CXCR5. Functionally, CD4+PD-1high T cells actively supported B-cell growth, while CD4+PD-1low T cells displayed a reduced cytokine production and cell-signal transduction. Clinically, we observed that the numbers of CD4+ or CD8+PD-1low T cells significantly correlate with a reduced overall survival in FL patients (P=0.007 and 0.04 respectively; n=32). In contrast, the number of CD4+PD-1high T cells was not associated with patient outcome. Taken together, these results indicated that PD-1 expression defines two sub-populations with distinct functions that differentially impact patient outcome in FL.

摘要翻译： 

为探究程序性死亡受体1（PD-1）在滤泡性淋巴瘤（FL）中的生物学及临床意义，我们对PD-1阳性T细胞亚群进行表征，并评估其生物学功能及潜在临床影响。研究发现PD-1以高/低两种强度表达于肿瘤内CD4阳性T细胞，代表两个不同的细胞亚群：免疫组化显示CD4阳性PD-1高表达T细胞主要定位于淋巴结滤泡区，而PD-1低表达T细胞则主要呈滤泡间分布。肿瘤内CD4阳性PD-1高表达T细胞具有滤泡辅助T细胞（TFH）表型，表达CXCR5、分泌IL-21、BCL-6阳性且不表达TIM-3；相比之下，CD4阳性PD-1低表达T细胞呈现耗竭表型，表达TIM-3而不表达BCL-6与CXCR5。功能学实验表明，CD4阳性PD-1高表达T细胞能有效支持B细胞增殖，而CD4阳性PD-1低表达T细胞则表现为细胞因子分泌能力下降和细胞信号转导减弱。临床数据分析显示，CD4阳性或CD8阳性PD-1低表达T细胞数量与FL患者总生存期缩短显著相关（分别为P=0.007和0.04；n=32），而CD4阳性PD-1高表达T细胞数量与患者预后无显著关联。综上结果表明，PD-1表达可界定两个功能迥异的T细胞亚群，二者对FL患者预后产生差异化影响。

原文链接：

PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival