Greenplate Allison R, Johnson Douglas B, Ferrell P Brent, Irish Jonathan M
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Eur J Cancer. 2016 Jul;61:77-84. doi: 10.1016/j.ejca.2016.03.085. Epub 2016 May 4.
Treatments that successfully modulate anti-cancer immunity have significantly improved outcomes for advanced stage malignancies and sparked intense study of the cellular mechanisms governing therapy response and resistance. These responses are governed by an evolving milieu of cancer and immune cell subpopulations that can be a rich source of biomarkers and biological insight, but it is only recently that research tools have developed to comprehensively characterize this level of cellular complexity. Mass cytometry is particularly well suited to tracking cells in complex tissues because >35 measurements can be made on each of hundreds of thousands of cells per sample, allowing all cells detected in a sample to be characterized for cell type, signalling activity, and functional outcome. This review focuses on mass cytometry as an example of systems level characterization of cancer and immune cells in human tissues, including blood, bone marrow, lymph nodes, and primary tumours. This review also discusses the state of the art in single cell tumour immunology, including tissue collection, technical and biological quality controls, computational analysis, and integration of different experimental and clinical data types. Ex vivo analysis of human tumour cells complements both in vivo monitoring, which generally measures far fewer features or lacks single cell resolution, and laboratory models, which incur cell type losses, signalling alterations, and genomic changes during establishment. Mass cytometry is on the leading edge of a new generation of cytomic tools that work with small tissue samples, such as a fine needle aspirates or blood draws, to monitor changes in rare or unexpected cell subsets during cancer therapy. This approach holds great promise for dissecting cellular microenvironments, monitoring how treatments affect tissues, revealing cellular biomarkers and effector mechanisms, and creating new treatments that productively engage the immune system to fight cancer and other diseases.
成功调节抗癌免疫的治疗方法显著改善了晚期恶性肿瘤的治疗效果，并引发了对控制治疗反应和耐药性的细胞机制的深入研究。这些反应受癌症和免疫细胞亚群不断变化的环境所支配，这些亚群可能是丰富的生物标志物来源和生物学见解，但直到最近研究工具才得以发展，以全面表征这种细胞复杂性水平。质谱流式细胞术特别适合于追踪复杂组织中的细胞，因为每个样本中数十万个细胞中的每一个都可以进行超过35项测量，从而能够对样本中检测到的所有细胞进行细胞类型、信号活性和功能结果的表征。本综述重点介绍质谱流式细胞术，作为对人体组织（包括血液、骨髓、淋巴结和原发性肿瘤）中的癌症和免疫细胞进行系统水平表征的一个例子。本综述还讨论了单细胞肿瘤免疫学的最新进展，包括组织采集、技术和生物学质量控制、计算分析以及不同实验和临床数据类型的整合。对人类肿瘤细胞的体外分析补充了体内监测（通常测量的特征要少得多或缺乏单细胞分辨率）和实验室模型（在建立过程中会出现细胞类型丢失、信号改变和基因组变化）。质谱流式细胞术处于新一代细胞组学工具的前沿，这些工具可用于处理小组织样本，如细针穿刺活检或采血样本，以监测癌症治疗期间罕见或意外细胞亚群的变化。这种方法对于剖析细胞微环境、监测治疗对组织的影响、揭示细胞生物标志物和效应机制以及开发能够有效激活免疫系统对抗癌症和其他疾病的新疗法具有巨大潜力。
