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低频率的 Vγ9Vδ2 T 细胞预示新诊断急性髓系白血病患者生存期较差

英文原题:Low frequency of Vγ9Vδ2 T cells predicts poor survival in newly diagnosed acute myeloid leukemia.

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Low frequency of Vγ9Vδ2 T cells predicts poor survival in newly diagnosed acute myeloid leukemia.

PubMed 2024/08/27(内容时间) Blood Adv Q1 · IF 7.7(JCR 2025)

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中文摘要

在几种肿瘤亚型中,与其他免疫亚群相比,Vγ9Vδ2 T细胞浸润增加已被证明具有最高的预后价值。在急性髓系白血病(AML)中,类似的发现仅基于转录组数据的推断,尚未针对混杂因素进行评估。

本研究旨在通过对初诊AML患者外周血进行免疫表型分析(流式或质谱流式),确定Vγ9Vδ2 T细胞频率的预后影响。该分析针对潜在混杂因素进行了校正(诊断时年龄、疾病状态、European LeukemiaNet分类、白细胞增多症,以及作为时间依赖性协变量的异基因造血干细胞移植)。队列由198例新诊断(ND)AML患者组成。通过单因素分析,诊断时Vγ9Vδ2 T细胞较低的患者5年总生存率和无复发生存率显著较低。这些结果在多因素分析中得到证实(风险比[HR],1.55 [95%置信区间(CI),1.04-2.30];P = .030和HR,1.64 [95% CI,1.06-2.53];P = .025)。在Vγ9Vδ2 T细胞较低的患者中观察到的免疫表型改变包括某些细胞毒性Vγ9Vδ2 T细胞亚群的丢失以及原始细胞表面butyrophilin 3A表达的降低。无论其Vγ9Vδ2 T细胞水平如何,样本均可扩增,并在体外表现出相似的效应功能。

本研究证实了ND AML患者淋巴细胞中Vγ9Vδ2 T细胞升高具有预后价值。这些结果为考虑旨在增强Vγ9Vδ2 T细胞反应的巩固方案提供了强有力的依据。

展开英文摘要原文

In several tumor subtypes, an increased infiltration of Vγ9Vδ2 T cells has been shown to have the highest prognostic value compared with other immune subsets. In acute myeloid leukemia (AML), similar findings have been based solely on the inference of transcriptomic data and have not been assessed with respect to confounding factors.

This study aimed at determining, by immunophenotypic analysis (flow or mass cytometry) of peripheral blood from patients with AML at diagnosis, the prognostic impact of Vγ9Vδ2 T-cell frequency. This was adjusted for potential confounders (age at diagnosis, disease status, European LeukemiaNet classification, leukocytosis, and allogeneic hematopoietic stem cell transplantation as a time-dependent covariate). The cohort was composed of 198 patients with newly diagnosed (ND) AML. By univariate analysis, patients with lower Vγ9Vδ2 T cells at diagnosis had significantly lower 5-year overall and relapse-free survivals.

These results were confirmed in multivariate analysis (hazard ratio [HR], 1. 55 [95% confidence interval (CI), 1. 04-2. 30]; P = . 030 and HR, 1. 64 [95% CI, 1. 06-2. 53]; P = . 025). Immunophenotypic alterations observed in patients with lower Vγ9Vδ2 T cells included a loss of some cytotoxic Vγ9Vδ2 T-cell subsets and a decreased expression of butyrophilin 3A on the surface of blasts. Samples expanded regardless of their Vγ9Vδ2 T-cell levels and displayed similar effector functions in vitro.

This study confirms the prognostic value of elevated Vγ9Vδ2 T cells among lymphocytes in patients with ND AML. These results provide a strong rationale to consider consolidation protocols aiming at enhancing Vγ9Vδ2 T-cell responses.

论文信息

作者
Le Floch AC、Orlanducci F、Béné MC、Ben Amara A、Rouviere MS、Salem N、Le Roy A、Cordier C
单位
Equipe Immunité et Cancer, Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, Marseille, France.France
文献类型
非美国政府资助研究
期刊
Blood advances2024 Aug 27
原文标识
PubMed 38788176 · DOI 10.1182/bloodadvances.2023011594