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Beyond tumor mutational burden: potential and limitations in using exosomes to predict response to immunotherapy.
Expert Review of Molecular Diagnostics ( IF 5.1 ) Pub Date : 2019-11-10 , DOI: 10.1080/14737159.2020.1688144
Jennifer Crow 1 , Glenson Samuel 2 , Andrew K Godwin 1, 3
Affiliation  

Introduction: Immune checkpoint blockade (ICB) has ushered in a new era of cancer therapeutics. The standard for determining which patients might benefit from ICB-based therapies is through the assessment of tumor mutational burden using formalin-fixed paraffin-embedded (FFPE) tumor tissue samples; however, this strategy is imperfect. The discovery of exosomal PD-L1 has placed these nano-vesicles to the forefront of immunotherapy biomarker development. Exosomes and other extracellular vesicles contain proteins and nucleic acids specific to their cell of origin and their production is increased in disease state such as cancer and can be isolated from most types of liquid biopsy. Given this opportunity, a large-scale bioengineering effort has centered on developing technologies capable of isolating distinct subsets of exosomes and interrogating their content for biomarker discovery.

Areas covered: This review investigates the current state of small extracellular vesicles (sEVs), focusing on exosomes, as they relate to biomarkers of IBC. We will discuss technologies being developed to both capture and evaluate exosomal cargo and as some of the challenges they face.

Expert opinion: The advancement of microfluidic technologies, along with rapidly evolving methodologies in RNAseq and proteomics, are making the potential of utilizing exosomes as prognostic and diagnostic biomarkers of ICB into a likely reality.



中文翻译:

超越肿瘤突变负担:使用外泌体预测对免疫治疗反应的潜力和局限性。

介绍:免疫检查站封锁(ICB)开创了癌症治疗的新时代。确定哪些患者可能受益于基于ICB的治疗的标准是通过使用福尔马林固定石蜡包埋(FFPE)肿瘤组织样品评估肿瘤突变负荷;但是,这种策略是不完善的。外泌体PD-L1的发现将这些纳米囊泡置于免疫疗法生物标志物开发的最前沿。外泌体和其他细胞外囊泡含有特定于其起源细胞的蛋白质和核酸,并且在疾病状态(例如癌症)中其产量增加,并且可以从大多数类型的液体活检中分离出来。有了这个机会

涵盖的领域:这篇综述调查了小细胞外囊泡(sEVs)的当前状态,重点关注囊泡,因为它们与IBC的生物标志物有关。我们将讨论为捕获和评估外泌体货物而开发的技术,以及它们所面临的一些挑战。

专家意见:微流体技术的发展,以及RNAseq和蛋白质组学方法的迅速发展,正在使利用外来体作为ICB的预后和诊断生物标志物的潜力成为现实。

更新日期:2019-11-10
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