Immune cell profiling in atherosclerosis: role in research and precision medicine.
Immune cell profiling in atherosclerosis: role in research and precision medicine.
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DOI：
10.1038/s41569-021-00589-2
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Giannarelli C
中科院分区：
文献类型：
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作者：
Fernandez DM;Giannarelli C
炎症密切参与动脉粥样硬化的所有阶段，并且在最佳治疗的患者中仍然是一个实质性的残余心血管风险因素。靶向炎症可减少有心肌梗死史患者的心血管事件的概念证明，突出了迫切需要确定新的免疫疗法来治疗动脉粥样硬化性心血管疾病患者。重要的是，来自新临床试验的新兴数据表明，动脉粥样硬化的成功免疫疗法需要针对不同患者群体的特定免疫改变进行调整。在这篇综述中，我们讨论了单细胞技术-如单细胞质量细胞计数，单细胞RNA测序和转录组和表位的细胞索引测序-是理想的映射人类动脉粥样硬化斑块的细胞和分子组成，以及这些数据如何可以帮助发现新的精确的免疫疗法。我们还认为，来自人类研究的单细胞数据需要在相关实验模型中进行严格验证，包括快速新兴的单细胞CRISPR筛选技术和动脉粥样硬化小鼠模型。最后，我们讨论了在药物开发的早期阶段实施单细胞免疫监测工具的重要性，以帮助精确选择目标患者人群，将数据驱动转化为随机临床试验，并将新的免疫疗法成功转化为临床。在这篇综述中，费尔南德斯和Giannarelli讨论了单细胞技术如何促进我们对动脉粥样硬化斑块的细胞和分子组成的理解，以及这些方法如何指导新的个性化免疫疗法和免疫监测工具的设计，用于动脉粥样硬化性心血管疾病患者的管理。动脉粥样硬化是由脂质的内皮下积聚引发的，脂质的内皮下积聚触发适应不良的、非消退的慢性炎症。近期急性心肌梗死患者中，抗炎干预已显著降低了不良心血管事件的风险。自2017年以来发表的临床试验数据显示，成功的治疗需要针对特定的患者群体进行量身定制。单细胞技术是研究免疫系统动力学的理想方法，可以促进我们对人类动脉粥样硬化组织的细胞和分子结构的理解，从而促进药物发现。在药物测试的早期阶段纳入单细胞免疫监测工具可以促进心血管疾病的药物发现和精准医学，以降低患者心血管不良结局和死亡的风险。
Inflammation is intimately involved at all stages of atherosclerosis and remains a substantial residual cardiovascular risk factor in optimally treated patients. The proof of concept that targeting inflammation reduces cardiovascular events in patients with a history of myocardial infarction has highlighted the urgent need to identify new immunotherapies to treat patients with atherosclerotic cardiovascular disease. Importantly, emerging data from new clinical trials show that successful immunotherapies for atherosclerosis need to be tailored to the specific immune alterations in distinct groups of patients. In this Review, we discuss how single-cell technologies — such as single-cell mass cytometry, single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing — are ideal for mapping the cellular and molecular composition of human atherosclerotic plaques and how these data can aid in the discovery of new precise immunotherapies. We also argue that single-cell data from studies in humans need to be rigorously validated in relevant experimental models, including rapidly emerging single-cell CRISPR screening technologies and mouse models of atherosclerosis. Finally, we discuss the importance of implementing single-cell immune monitoring tools in early phases of drug development to aid in the precise selection of the target patient population for data-driven translation into randomized clinical trials and the successful translation of new immunotherapies into the clinic. In this Review, Fernandez and Giannarelli discuss how single-cell technologies can advance our understanding of the cellular and molecular composition of atherosclerotic plaques and how these approaches can guide the design of new, personalized immunotherapies and immune monitoring tools for the management of patients with atherosclerotic cardiovascular disease. Atherosclerosis is initiated by the subendothelial accumulation of lipids that trigger maladaptive, non-resolving, chronic inflammation. Anti-inflammatory interventions have substantially reduced the risk of adverse cardiovascular events in patients with recent acute myocardial infarction. Emerging data from clinical trials published since 2017 show that successful treatments need to be tailored to specific groups of patients. Single-cell technologies are ideal for studying immune system dynamics and can advance our understanding of the cellular and molecular architecture of human atherosclerotic tissue to advance drug discovery. The inclusion of single-cell immune-monitoring tools in early phases of drug testing could advance drug discovery and precision medicine in cardiovascular disease to reduce the risk of adverse cardiovascular outcomes and death in patients.
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影响因子：
16.8
作者：
Bendall SC;Nolan GP;Roederer M;Chattopadhyay PK
通讯作者：
Chattopadhyay PK
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
64.5
作者：
Dixit, Atray;Pamas, Oren;Li, Biyu;Chen, Jenny;Fulco, Charles P.;Jerby-Amon, Livnat;Marjanovic, Nemanja D.;Dionne, Danielle;Burks, Tyler;Raychowdhury, Raktima;Adamson, Britt;Norman, Thomas M.;Lander, Eric S.;Weissman, Jonathan S.;Friedman, Nir;Regev, Aviv
通讯作者：
Regev, Aviv
影响因子：
16.6
作者：
Abolins S;King EC;Lazarou L;Weldon L;Hughes L;Drescher P;Raynes JG;Hafalla JCR;Viney ME;Riley EM
通讯作者：
Riley EM
影响因子：
82.9
作者：
通讯作者：
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