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急性髓系白血病患者中 PD-1(+)Foxp3(+) γδ T 细胞增多与较差的总生存期相关

英文原题:Increased PD-1(+)Foxp3(+) γδ T cells associate with poor overall survival for patients with acute myeloid leukemia.

查看英文原题

Increased PD-1(+)Foxp3(+) γδ T cells associate with poor overall survival for patients with acute myeloid leukemia.

PubMed 2022/12/15(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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研究概要

AML 中 PD-1 + Foxp3 + γδ T 细胞亚群的显著增加与不良临床结局相关,这为 AML 患者的研究提供了预测价值。

中文摘要

γδ T细胞在免疫治疗的抗白血病作用中至关重要,但γδ T细胞包含不同功能亚群,其中包括表达Foxp3的调节性细胞亚群。在急性髓系白血病(AML)患者中,这些亚群是否与免疫检查点介导的T细胞免疫功能障碍相关,尚不清楚。

研究者使用TCGA队列167例患者的RNA测序数据,分析PD-1与FOXP3基因之间的相关性及其与AML患者预后的关系;采用流式细胞术检测γδ T细胞及Vδ1、Vδ2两个亚群中Foxp3阳性和/或PD-1阳性细胞的比例,并对磁珠分选的外周血γδ T细胞中的FOXP3和PD-1基因进行实时定量PCR分析。

TCGA数据中,PD-1基因与FOXP3基因呈正相关,两者高水平共表达与总生存期(OS)较差相关。AML患者γδ T细胞分布失衡,Vδ1亚群增加而Vδ2亚群减少。与健康人相比,新诊断AML患者中PD-1阳性γδ T细胞、Foxp3阳性γδ T细胞以及PD-1和Foxp3双阳性γδ T细胞的比例均显著升高。更重要的是,PD-1和Foxp3双阳性γδ T细胞较多的AML患者OS较短,该亚群可能成为白血病免疫治疗的潜在靶点。

AML患者PD-1和Foxp3双阳性γδ T细胞亚群显著增加,并与较差临床结局相关,可为AML患者研究提供预后预测价值。

展开英文摘要原文

In this study, we used RNA-seq data from 167 patients in TCGA dataset to analyze the correlation between PD-1 and FOXP3 genes and these two genes' association with the prognosis of AML patients. The expression proportion of Foxp3 + /PD-1 + cells in γδ T cells and two subgroups Vδ1 and Vδ2 T cells were performed by flow cytometry. The expression level of FOXP3 and PD-1 genes in γδ T cells were sorted from peripheral blood by MACS magnetic cell sorting technique were analyzed by quantitative real-time PCR.

We found that PD-1 gene was positively correlated with FOXP3 gene and highly co-expressed PD-1 and FOXP3 genes were associated with poor overall survival (OS) from TCGA database. Then, we detected a skewed distribution of γδ T cells with increased Vδ1 and decreased Vδ2 T cell subsets in AML. Moreover, significantly higher percentages of PD-1 + γδ, Foxp3 + γδ, and PD-1 + Foxp3 + γδ T cells were detected in de novo AML patients compared with healthy individuals. More importantly, AML patients containing higher PD-1 + Foxp3 + γδ T cells had lower OS, which might be a potential therapeutic target for leukemia immunotherapy.

A significant increase in the PD-1 + Foxp3 + γδ T cell subset in AML was associated with poor clinical outcome, which provides predictive value for the study of AML patients.

论文信息

作者
Zheng J、Qiu D、Jiang X、Zhao Y、Zhao H、Wu X、Chen J、Lai J
单位
Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.China
期刊
Frontiers in oncology2022
原文标识
PubMed 36591503 · DOI 10.3389/fonc.2022.1007565