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文章:

肿瘤微环境中T细胞表型(包括CD57阳性滤泡辅助性T细胞)与滤泡性淋巴瘤不良预后相关

T-cell phenotype including CD57+ T follicular helper cells in the tumor microenvironment correlate with a poor outcome in follicular lymphoma

原文发布日期:2023-08-18

DOI: 10.1038/s41408-023-00899-3

类型: Article

开放获取: 是

 

英文摘要:

T-lymphocytes are prevalent in the tumor microenvironment of follicular lymphoma (FL). However, the phenotype of T-cells may vary, and the prevalence of certain T-cell subsets may influence tumor biology and patient survival. We therefore analyzed a cohort of 82 FL patients using CyTOF to determine whether specific T-cell phenotypes were associated with distinct tumor microenvironments and patient outcome. We identified four immune subgroups with differing T-cell phenotypes and the prevalence of certain T-cell subsets was associated with patient survival. Patients with increased T cells with early differentiation stage tended to have a significantly better survival than patients with increased T-cells of late differentiation stage. Specifically, CD57+ TFH cells, with a late-stage differentiation phenotype, were significantly more abundant in FL patients who had early disease progression and therefore correlated with an inferior survival. Single cell analysis (CITE-seq) revealed that CD57+ TFH cells exhibited a substantially different transcriptome from CD57− TFH cells with upregulation of inflammatory pathways, evidence of immune exhaustion and susceptibility to apoptosis. Taken together, our results show that different tumor microenvironments among FL patients are associated with variable T-cell phenotypes and an increased prevalence of CD57+ TFH cells is associated with poor patient survival.
 

摘要翻译: 

T淋巴细胞在滤泡性淋巴瘤(FL)的肿瘤微环境中普遍存在。然而,T细胞的表型可能存在差异,特定T细胞亚群的丰度可能影响肿瘤生物学及患者生存。因此,我们通过使用CyTOF技术对82例FL患者队列进行分析,以探究特定T细胞表型是否与不同的肿瘤微环境及患者预后相关。我们鉴定出四个具有不同T细胞表型的免疫亚群,并且某些T细胞亚群的丰度与患者生存相关。T细胞处于早期分化阶段的患者往往比晚期分化阶段T细胞增多的患者生存期显著更长。具体而言,具有晚期分化表型的CD57+滤泡辅助性T细胞在早期疾病进展的FL患者中显著增多,因此与较差的生存率相关。单细胞分析(CITE-seq)显示,CD57+滤泡辅助性T细胞的转录组与CD57−滤泡辅助性T细胞存在显著差异,表现为炎症通路上调、免疫耗竭迹象以及对细胞凋亡的易感性增加。综上所述,我们的研究结果表明,FL患者中不同的肿瘤微环境与T细胞表型的差异相关,而CD57+滤泡辅助性T细胞的增多与患者不良生存相关。

 

原文链接:

T-cell phenotype including CD57+ T follicular helper cells in the tumor microenvironment correlate with a poor outcome in follicular lymphoma

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