在几种肿瘤亚型中，与其他免疫亚型相比，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，并且尚未针对混杂因素进行评估。本研究旨在通过对诊断时 AML 患者的外周血进行免疫表型分析（流式或质谱细胞术）来确定 Vγ9Vδ2 T 细胞频率的预后影响。针对潜在的混杂因素（诊断年龄、疾病状态、欧洲白血病网分类、白细胞增多和同种异体造血干细胞移植作为时间依赖性协变量）进行了调整。该队列由 198 名新诊断的 AML 患者组成。通过单变量分析，诊断时 Vγ9Vδ2 T 细胞较低的患者的 5 年总体生存率和无复发生存率显着较低。这些结果在多变量分析中得到证实（风险比 [HR]=1.55[1.04-2.30]，p=0.030 和 HR=1.64[1.06, 2.53]，p=0.025）。在 Vγ9Vδ2 T 细胞较低的患者中观察到的免疫表型改变包括一些细胞毒性 Vγ9Vδ2 T 细胞亚群的丢失以及原始细胞表面 BTN3A 表达的降低。无论 Vγ9Vδ2 T 细胞水平如何，样品都会扩增，并在体外表现出相似的效应功能。这项研究证实了淋巴细胞中 Vγ9Vδ2 T 细胞升高对新诊断的 AML 患者的预后价值。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理由。版权所有 © 2024 美国血液学会。

In several tumor subtypes, increased infiltration of Vγ9Vδ2 T-cells has been shown to have the highest prognostic value compared to 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 AML patients 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 newly diagnosed AML patients. 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[1.04-2.30], p=0.030 and HR=1.64[1.06, 2.53], p=0.025). 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 BTN3A 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 newly diagnosed AML patients. These results provide a strong rationale to consider consolidation protocols aiming at enhancing Vγ9Vδ2 T-cell responses.Copyright © 2024 American Society of Hematology.