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外周血免疫特征分析揭示初诊 NK/T 细胞淋巴瘤患者的关键特征

英文原题:Peripheral blood immune profiling reveals key signatures in newly diagnosed NK/T cell lymphoma patients.

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Peripheral blood immune profiling reveals key signatures in newly diagnosed NK/T cell lymphoma patients.

PubMed 2026/06/17(内容时间) Theranostics Q1 · IF 14.9(JCR 2025)

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研究概要

我们揭示了新诊断 NK/T 细胞淋巴瘤患者 PBMC 的动态变化,并鉴定了细胞内 EBV 高载量患者的特异性特征。我们的发现为 NKTCL 的免疫发病机制提供了新见解,为基于免疫的分层及治疗策略的开发提供了有价值的信息。

研究思路结论见上方概要

自然杀伤/T细胞淋巴瘤(NKTCL)是一种侵袭性EB病毒(EBV)相关非霍奇金淋巴瘤,预后较差。近期对肿瘤组织的基因组学和转录组学研究增进了我们对NKTCL发病机制的理解,但初诊时的全身免疫特征仍未完全阐明。

本研究通过单细胞RNA测序对20例新诊断NKTCL患者和12例健康供者的外周血单个核细胞(PBMCs)免疫图谱进行了表征,并通过流式细胞术和PrimeFlow验证了结果。

我们在NKTCL中鉴定出一个独特的增殖性NK/T(Proli-NK/T)细胞亚群,其特征为细胞周期相关基因高表达,但缺乏恶性表型。此外,我们观察到总B细胞和经典记忆B细胞减少,并伴有凋亡和细胞分化特征的富集。NK细胞显示HLA II类和活化标志物表达增加,同时与CD4 + T细胞的预测相互作用增强。初始CD4 + T细胞的减少可能意味着其向Th1和Th17细胞的分化偏移,而表达颗粒酶K(GZMK +)的CD8 + 中央记忆T细胞的扩增与干扰素-γ驱动的反应相关。细胞内EBV载量高的患者表现出高细胞毒性CD56 dim _PTPRCAP NK细胞和GZMK + GZMB + CD8 + 效应记忆T细胞的积累,同时伴有记忆B细胞的显著耗竭。这提示细胞内EBV负荷与NKTCL中外周免疫失调之间存在相关性。

展开英文摘要原文

In this study, we characterized the immune landscape of peripheral blood mononuclear cells (PBMCs) from 20 newly diagnosed NKTCL patients and 12 healthy donors using single-cell RNA sequencing and confirmed our results through flow cytometry and PrimeFlow.

We identified a distinct proliferative-NK/T (Proli-NK/T) cell subset in NKTCL, characterized by high expression of cell cycle-related genes but lacking a malignant phenotype. Additionally, we observed a reduction in total and classical memory B cells, accompanied by enrichment of apoptosis and cell differentiation signatures. NK cells showed increased expression of HLA class II and activation markers, along with enhanced predicted interactions with CD4 + T cells. The decrease of naive CD4 + T cells might imply their skewed differentiation into Th1 and Th17 cells, while expansion of granzyme K (GZMK + )-expressing CD8 + central memory T cells was associated with interferon-γ-driven responses. Patients with a high intracellular EBV load exhibited accumulation of highly cytotoxic CD56 dim _PTPRCAP NK cells and GZMK + GZMB + CD8 + effector memory T cells, along with a marked depletion of memory B cells. This implies a correlation between intracellular EBV burden and peripheral immune dysregulation in NKTCL.

We have uncovered the dynamic changes in PBMCs of newly diagnosed NK/T cell lymphoma patients and identified specific characteristics in patients with high intracellular EBV levels. Our findings provide new insights into the immunopathogenesis of NKTCL, offering valuable information for immune-based stratification and the development of therapeutic strategies.

论文信息

作者
Li D、Zou H、Wang M、Tian N、Liu C、Zhang W、Jiang S、Zhu R
第一作者单位
Department of Lymphoma and Medical Oncology, Fudan University Shanghai Cancer Center, Research Center for Lymphoma, Fudan University, Shanghai 200032, China.China
通讯作者单位
University of Chinese Academy of Sciences, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China.China
期刊
Theranostics2026
原文标识
PubMed 42370195 · DOI 10.7150/thno.132582