Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events-A Comprehensive Review.

Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events-A Comprehensive Review.
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检查点抑制剂诱导的免疫相关不良事件的生物标志物--综述。

DOI:
10.3389/fonc.2020.585311
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发表时间:
2020
影响因子:
4.7
通讯作者:
Hamann D
Hamann D
中科院分区:
医学3区
文献类型:
--
作者:
Hommes JW;Verheijden RJ;Suijkerbuijk KPM;Hamann D

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免疫检查点抑制剂(ICIs)显着改善了不同类型癌症患者的预后。通过阻断细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 和程序性细胞死亡蛋白 1 (PD-1),免疫系统的负反馈机制受到抑制,从而可能产生非常持久的抗肿瘤反应。尽管 ICI 前景广阔,但它也会引发自身免疫毒性。这些免疫相关不良事件 (irAE) 可能很严重,有时甚至致命。因此,能够预测患者的严重 irAE 将对临床决策具有附加价值。使用“不良事件”、“免疫检查点抑制剂”、“生物标志物”和 PubMed 中的同义词进行搜索,产生 3580 个搜索结果。在筛选标题和摘要与评论问题的相关性、报告的潜在生物标志物的统计显着性以及对剩余全文的评估后,纳入了 35 篇文章。通过引用和使用 PubMed 上的类似文章功能获得了另外 5 份报告。目前的知识以综合表格形式呈现,总结了在 ICI 治疗之前和期间预测 irAE 的基于血液、免疫遗传学和微生物生物标志物。到目前为止,还没有任何一种生物标志物被证明能够充分预测 irAE 的发展。提出了对该主题进一步研究的建议。
Immune checkpoint inhibitors (ICIs) have substantially improved the prognosis of patients with different types of cancer. Through blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), negative feedback mechanisms of the immune system are inhibited, potentially resulting in very durable anti-tumor responses. Despite their promise, ICIs can also elicit auto-immune toxicities. These immune-related adverse events (irAEs) can be severe and sometimes even fatal. Therefore, being able to predict severe irAEs in patients would be of added value in clinical decision making. A search was performed using “adverse events”, “immune checkpoint inhibitor”, “biomarker”, and synonyms in PubMed, yielding 3580 search results. After screening title and abstract on the relevance to the review question, statistical significance of reported potential biomarkers, and evaluation of the remaining full papers, 35 articles were included. Five additional reports were obtained by means of citations and by using the similar article function on PubMed. The current knowledge is presented in comprehensive tables summarizing blood-based, immunogenetic and microbial biomarkers predicting irAEs prior to and during ICI therapy. Until now, no single biomarker has proven to be sufficiently predictive for irAE development. Recommendations for further research on this topic are presented.
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