Extracellular Vesicle-Derived Protein File from Peripheral Blood Predicts Immune-Related Adverse Events in Gastric Cancer Patients Receiving Immunotherapy.
Extracellular Vesicle-Derived Protein File from Peripheral Blood Predicts Immune-Related Adverse Events in Gastric Cancer Patients Receiving Immunotherapy.
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外周血细胞外囊泡衍生的蛋白质文件可预测接受免疫治疗的胃癌患者的免疫相关不良事件。
作者：
大多数胃癌（GC）患者已经从免疫检查点抑制剂中获益，但其中一些患者可能会因免疫相关不良事件（irAE）而终止免疫治疗。细胞外囊泡可以携带蛋白质、核酸等生物大分子进入受体细胞，这对于探索通过EV衍生蛋白作为irAE生物标志物的潜力具有重要意义。在62例GC患者中，从42种重要蛋白中筛选EV-ICOS和EV-IDO 1作为irAE的生物标志物，然后在40例GC患者的验证队列中进行确认。总之，EV-ICOS和EV-IDO 1可以很好地预测ICI治疗的GC患者的irAE。免疫检查点抑制剂（ICI）开启了胃癌（GC）治疗的新阶段，许多患者已经从ICI中受益。液体活检推动GC精准医学发展。然而，由于缺乏免疫相关不良事件（irAE）的精确生物标志物，不能保证接受ICIs治疗的GC患者的安全性。在我们的研究中，纳入了接受ICI治疗的GC患者，以研究ICI的irAE与相应结局之间的相关性。我们还通过EV衍生蛋白探索了irAE生物标志物的潜力。动态血浆取自回顾性或前瞻性生成的102例ICIs治疗的GC患者，这些患者被分为发现和验证队列。描述了血浆EV衍生的蛋白质谱，并从42种重要蛋白质中筛选出两种EV蛋白质，诱导性T细胞共刺激因子（EV-ICOS）和吲哚胺2，3-双加氧酶1（EV-IDO 1），以预测伴有irAE的ICI的预后。我们的工作首次提出EV蛋白可以预测ICIs对应的irAE，这将有助于GC患者的诊断和治疗，并方便受益者的筛选。
Most gastric cancer (GC) patients have already benefited from immune checkpoint inhibitors, but some of them may terminate immunotherapy due to immune-related adverse events (irAEs). Extracellular vesicles have been shown to carry proteins, nucleic acids and other biomacromolecules to recipient cells, which is very important for exploring the potential of biomarkers of irAEs via EV-derived proteins. In 62 GC patients, EV-ICOS and EV-IDO1 were screened from 42 vital proteins as biomarkers of irAEs, and then confirmed in a validating cohort of 40 GC patients. In summary, EV-ICOS and EV-IDO1 can perfectly predict irAEs of ICI treated GC patients. Immune checkpoint inhibitors (ICIs) initiate a new stage for gastric cancer (GC) therapeutics, and plenty of patients have already benefited from ICIs. Liquid biopsy promotes the development of precision medicine of GC. However, due to the lack of precision biomarkers of immune-related adverse events (irAEs), the safety of ICIs-treated GC patients cannot be guaranteed. In our study, GC patients treated with ICIs were included for investigating the correlation between irAEs of ICIs and corresponding outcomes. We also explored the potential of biomarkers of irAEs via EV-derived proteins. Dynamic plasma was taken from 102 ICIs-treated GC patients generated retrospectively or prospectively, who were divided into discovery and validating cohorts. Plasma EV-derived protein profiles were described, and two EV-proteins, inducible T-cell co-stimulator (EV-ICOS) and indoleamine 2,3-dioxygenase 1(EV-IDO1), from 42 vital proteins were screened to predict the prognosis of ICIs with irAEs. Our work is the first to propose that EV-proteins can predict ICIs-corresponding irAEs, which can be conducive to the diagnosis and treatment of GC patients, and to facilitate the screening of beneficiaries.
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