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免疫检查点阻断以剂量依赖的方式降低了幼稚 T 细胞对药物相关抗原的初始激活阈值。

Immune checkpoint blockade lowers the threshold of naïve T-cell priming to drug-associated antigens in a dose-dependent fashion.

机构信息

Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool L69 3GE, United Kingdom.

Clinical Pharmacology and Safety Science, AstraZeneca, Cambridge, United Kingdom.

出版信息

Toxicol Sci. 2024 Nov 1;202(1):13-18. doi: 10.1093/toxsci/kfae118.

Abstract

A growing body of clinical and experimental evidence indicates that immune checkpoint blockade enhances patient susceptibility to hypersensitivity reactions to co-administered medications. In this study, we utilized an in vitro T-cell priming assay to demonstrate one of the mechanistic hypotheses on how this occurs; through lowering of the threshold in patients to elicit aberrant T-cell responses. We outline the dependency of de novo T-cell priming responses to drug-associated antigens on dose at initial exposure. Findings support the aforementioned hypothesis and offer an experimental representation of fundamental parameters at play in hypersensitivity reactions to low molecular weight compounds.

摘要

越来越多的临床和实验证据表明,免疫检查点阻断会增强患者对同时使用的药物产生过敏反应的易感性。在这项研究中,我们利用体外 T 细胞致敏测定来证明其中一种发生机制假说;即通过降低患者引发异常 T 细胞反应的阈值。我们概述了初始暴露时药物相关抗原的新 T 细胞致敏反应对剂量的依赖性。研究结果支持了上述假说,并为低分子量化合物过敏反应中起作用的基本参数提供了实验表现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b2c/11514829/31c84c620be8/kfae118f1.jpg

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