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急性髓系白血病中的细胞毒性 T 淋巴细胞:监测预后和指导治疗选择。

Cytotoxic T-lymphocytes in acute myeloid leukemia: Monitoring prognosis and guiding treatment choice.

机构信息

Department of Clinical Laboratory, Beilun People's Hospital, Beilun Branch of the First Affiliated Hospital, School of Medicine, Zhejiang University, Ningbo, China.

Department of Obstetrics, Beilun People's Hospital, Beilun Branch of the First Affiliated Hospital, School of Medicine, Zhejiang University, Ningbo, China.

出版信息

J Gene Med. 2024 Jan;26(1):e3587. doi: 10.1002/jgm.3587. Epub 2023 Sep 11.

Abstract

BACKGROUND

Cytotoxic T-lymphocyte (CTL)-mediated therapy has become the central theme of cancer immunotherapy. The present study emphasized the role of CTLs in acute myeloid leukemia (AML) and aimed to understand the role of CTLs cytogenetic markers in monitoring AML prognostic outcomes and clinical treatment responses.

METHODS

Seurat was employed to analyze single-cell RNA sequencing data in GSE116256. CellChat was used to detect cell-cell interactions to determine the central role of CTLs. The marker genes of CTLs were extracted and randomForestSRC was employed to construct a random forest model. The prognosis, immune checkpoint expression, immune cell infiltration, immunotherapy response and drug sensitivity of AML patients were evaluated according to the model.

RESULTS

Seven types of cellular components of AML were identified in GSE116256, and CTLs radiated the most interactions with other cell types. Random forest analysis screened out six marker genes for construction of the model. The risk score calculated according to the model was positively correlated with immune score, immune cell infiltration, expression of multiple immune checkpoints and immune effect pathway. The response rate of immunotherapy was significantly higher and more sensitive to 14 drugs in high-risk samples than in low-risk samples, whereas low-risk patients showed a higher sensitivity to six drugs.

CONCLUSIONS

The present study emphasized the central role of CTLs in cell communication and established a random forest regression model based on its cytogenetic markers, which helps to stratify the prognosis of AML, promotes the understanding of the phenotype of AML and may also guide the treatment choice of AML patients, which contributed to stratification of AML prognosis, promoted understanding of the phenotype of AML and may guide treatment selection in patients with AML.

摘要

背景

细胞毒性 T 淋巴细胞(CTL)介导的治疗已成为癌症免疫治疗的核心主题。本研究强调 CTL 在急性髓系白血病(AML)中的作用,并旨在了解 CTL 细胞遗传学标志物在监测 AML 预后结果和临床治疗反应中的作用。

方法

使用 Seurat 分析 GSE116256 中的单细胞 RNA 测序数据。使用 CellChat 检测细胞间相互作用,以确定 CTL 的核心作用。提取 CTL 的标记基因,并使用随机森林 SRC 构建随机森林模型。根据该模型评估 AML 患者的预后、免疫检查点表达、免疫细胞浸润、免疫治疗反应和药物敏感性。

结果

在 GSE116256 中鉴定出 AML 的七种细胞成分,CTL 与其他细胞类型的相互作用最多。随机森林分析筛选出用于构建模型的六个标记基因。根据模型计算的风险评分与免疫评分、免疫细胞浸润、多个免疫检查点和免疫效应途径的表达呈正相关。高风险样本的免疫治疗反应率明显更高,对 14 种药物更敏感,而低风险样本对 6 种药物的敏感性更高。

结论

本研究强调了 CTL 在细胞通讯中的核心作用,并基于其细胞遗传学标志物建立了随机森林回归模型,有助于对 AML 进行预后分层,促进对 AML 表型的理解,并且可能指导 AML 患者的治疗选择。

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