免疫检查点 PD1/PDL1、TIM3/GAL9 和关键免疫介质景观揭示了伊马替尼对慢性髓性白血病反应的不同表达动态。

IF 3 3区 医学 Q2 HEMATOLOGY
María Jazmín Toloza, Marco Lincango, María Fernanda Camacho, Martin Manuel Ledesma, Alicia Enrico, Beatriz Moiraghi, Fernanda Tosin, Romina Mariano, Mariel Pérez, Pedro Negri Aranguren, María Elisa Riva, Irene B Larripa, Carolina B Belli
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引用次数: 0

摘要

慢性髓性白血病(CML)患者的免疫系统严重受损,阻碍了抗肿瘤反应,最大的免疫恢复发生在对酪氨酸激酶抑制剂产生深度分子反应之后。本研究旨在鉴别伊马替尼治疗最初一年中NCR2、IL2、IL4、EOMES、FOXP3、GATA3、RORGT、PD1/PDL1和TIM3/GAL9的表达模式,将我们之前的数据集扩展到19个关键免疫介质。我们对来自 89 名 CML 患者(包括 43 名纵向监测者)和 52 名健康捐献者的 171 份外周血样本进行了基因表达动态评估。单变量分析和无监督分析证实,除 TNF、ARG1 和 IL4 外,大多数研究的免疫介质的表达量都有所下降,基线样本和 3 个月样本之间存在差异。大多数研究的介质在治疗过程中趋于正常,TNF和IL6水平在3个月时短暂上升,尤其是在最佳应答者(BCR::ABL1
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Immune checkpoints PD1/PDL1, TIM3/GAL9 and key immune mediators landscape reveal differential expression dynamics on imatinib response in chronic myeloid leukemia.

The immune system of chronic myeloid leukemia (CML) patients is severely impaired, hampering anti-tumor responses, and maximal immune recovery occurs after achieving deep molecular responses to tyrosine kinase inhibitors. This study aimed to discern the expression patterns of NCR2, IL2, IL4, EOMES, FOXP3, GATA3, RORGT, PD1/PDL1 and TIM3/GAL9, expanding our previous dataset up to 19 key immune mediators, during the initial year on imatinib. Gene expression dynamics were evaluated in 171 peripheral blood samples from 89 CML patients, including 43 longitudinally monitored individuals, and 52 healthy donors. Univariate and unsupervised analyses confirmed diminished expression of most studied immune mediators, except for TNF, ARG1 and IL4, differentiating between baseline and 3-month samples. Most of the studied mediators normalized along treatment, with a transient increase of TNF and IL6 levels at 3-months, especially in optimal responders (BCR::ABL1 < 0.1%). Univariate and multivariate analyses showed heightened ARG1 levels and a transition from PD1/PDL1 dominance at 3 months to TIM3/GAL9 at 12 months in non-optimal responders (BCR::ABL1 ≥ 0.1%). Our longitudinal design offers a deeper exploration of immune gene expression dynamics in CML patients on imatinib, highlighting its potential implications for therapy outcomes.

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来源期刊
Annals of Hematology
Annals of Hematology 医学-血液学
CiteScore
5.60
自引率
2.90%
发文量
304
审稿时长
2 months
期刊介绍: Annals of Hematology covers the whole spectrum of clinical and experimental hematology, hemostaseology, blood transfusion, and related aspects of medical oncology, including diagnosis and treatment of leukemias, lymphatic neoplasias and solid tumors, and transplantation of hematopoietic stem cells. Coverage includes general aspects of oncology, molecular biology and immunology as pertinent to problems of human blood disease. The journal is associated with the German Society for Hematology and Medical Oncology, and the Austrian Society for Hematology and Oncology.
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