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.

炎症与动脉粥样硬化的所有阶段密切相关，并且在经过最佳治疗的患者中仍然是一个重要的残余心血管危险因素。针对炎症可减少有心肌梗死病史的患者的心血管事件的概念证明突出表明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数据表明，成功的动脉粥样硬化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——例如单细胞质谱流式细胞术，单细胞 RNA 测序和通过测序对转录组和表位进行细胞索引——非常适合绘制人类动脉粥样硬化斑块的细胞和分子组成，以及这些数据如何帮助发现新的精确免疫疗法。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得到严格验证，包括迅速兴起的单细胞 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群体，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.