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酪氨酸激酶抑制剂达沙替尼引发 NK 细胞对癌症、HIV 感染和衰老的细胞毒性的免疫调节活性

英文原题:Immunomodulatory Activity of the Tyrosine Kinase Inhibitor Dasatinib to Elicit NK Cytotoxicity against Cancer, HIV Infection and Aging.

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Immunomodulatory Activity of the Tyrosine Kinase Inhibitor Dasatinib to Elicit NK Cytotoxicity against Cancer, HIV Infection and Aging.

PubMed 2023/03/11(内容时间) Pharmaceutics Q1 · IF 6.9(JCR 2025)

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中文摘要

酪氨酸激酶抑制剂(TKIs)已被广泛用于治疗慢性髓性白血病(CML)。达沙替尼是一种广谱TKI,其脱靶效应赋予其免疫调节能力,从而增强针对癌细胞和病毒感染细胞的先天免疫反应。多项研究报道,达沙替尼可扩增记忆样自然杀伤(NK)细胞和γδ T细胞,这些细胞与停药后CML控制增强相关。在HIV感染背景下,这些先天细胞与病毒控制和保护相关,提示达沙替尼可能在改善CML和HIV结局方面具有潜在作用。此外,达沙替尼还可直接诱导衰老细胞凋亡,是一种新的潜在senolytic药物。在此,我们深入综述了与该药物相关的强效细胞毒性反应发展相关的病毒学和免疫遗传学因素的当前认识。此外,我们将讨论其针对CML、HIV感染和衰老的潜在治疗作用。

展开英文摘要原文

Tyrosine kinase inhibitors (TKIs) have been extensively used as a treatment for chronic myeloid leukemia (CML). Dasatinib is a broad-spectrum TKI with off-target effects that give it an immunomodulatory capacity resulting in increased innate immune responses against cancerous cells and viral infected cells.

Several studies reported that dasatinib expanded memory-like natural killer (NK) cells and γδ T cells that have been related with increased control of CML after treatment withdrawal. In the HIV infection setting, these innate cells are associated with virus control and protection, suggesting that dasatinib could have a potential role in improving both the CML and HIV outcomes.

Moreover, dasatinib could also directly induce apoptosis of senescence cells, being a new potential senolytic drug.

Here, we review in depth the current knowledge of virological and immunogenetic factors associated with the development of powerful cytotoxic responses associated with this drug. Besides, we will discuss the potential therapeutic role against CML, HIV infection and aging.

论文信息

作者
Rodríguez-Agustín A、Casanova V、Grau-Expósito J、Sánchez-Palomino S、Alcamí J、Climent N
单位
HIV Unit, Hospital Clínic-IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.Spain
文献类型
综述
期刊
Pharmaceutics2023 Mar 11
原文标识
PubMed 36986778 · DOI 10.3390/pharmaceutics15030917