Department of Dermatology, Henry Ford Health System, Detroit, Michigan, USA; Center for Cutaneous Biology and Immunology, Henry Ford Health System, Detroit, Michigan, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA.
Center for Cutaneous Biology and Immunology, Henry Ford Health System, Detroit, Michigan, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA; Wayne State University School of Medicine, Detroit, Michigan, USA.
J Invest Dermatol. 2021 Apr;141(4):705-712.e1. doi: 10.1016/j.jid.2020.12.008.
Traditional immunohistochemistry (IHC) is inherently limited by its ability to analyze only several markers within a histological tissue section at a given time, which hinders in-depth characterization and phenotyping of tissues. Imaging mass cytometry (IMC), which combines IHC using metal-labeled antibodies with laser ablation and detection using mass cytometry by time-of-flight, overcomes this limitation with the capability to simultaneously analyze up to 40 protein markers to generate high-dimensional images from a single tissue section. IMC analysis preserves tissue architecture and spatial cellular relationships that would otherwise be lost or significantly altered in applications requiring tissue dissociation, such as flow cytometry or single-cell RNA sequencing. Resulting high-dimensional histological images permit spatially conserved analysis to identify unique cell populations, cellular interactions and avoidances, and insight into activation and behavioral status based on tissue location. IMC can be performed on both frozen and formalin-fixed paraffin-embedded tissue, allowing for previously banked samples to be analyzed and correlated with known clinical outcomes. Expectedly, IMC will change the landscape of investigative pathology, particularly when used in coordination with multiomic platforms to combine transcriptomic and proteomic data at a single-cell resolution. Here, we aim to highlight the potential utility of IMC within dermatologic research and clinical applications.
传统的免疫组织化学(IHC)在分析组织切片中的标志物时存在固有的局限性,因为一次只能分析几个标志物,这限制了对组织的深入特征分析和表型分析。成像质谱流式细胞术(IMC)克服了这一限制,它将使用金属标记抗体的 IHC 与激光消融和飞行时间质谱流式细胞术检测相结合,能够同时分析多达 40 种蛋白质标志物,从而从单个组织切片生成高维图像。IMC 分析保留了组织架构和空间细胞关系,如果在需要组织解离的应用中,如流式细胞术或单细胞 RNA 测序,这些组织架构和空间细胞关系将丢失或发生显著改变。生成的高维组织学图像允许进行空间保守分析,以识别独特的细胞群、细胞相互作用和回避,并根据组织位置深入了解激活和行为状态。IMC 可在冷冻和福尔马林固定石蜡包埋组织上进行,这使得以前保存的样本能够进行分析,并与已知的临床结果相关联。可以预期,IMC 将改变研究病理学的格局,特别是在与多组学平台结合使用时,可在单细胞分辨率下结合转录组和蛋白质组数据。在这里,我们旨在强调 IMC 在皮肤科研究和临床应用中的潜在用途。