Characterizing Phenotypes and Signaling Networks of Single Human Cells by Mass Cytometry

Leelatian, Nalin; Diggins, Kirsten E.; Irish, Jonathan M.

doi:10.1007/978-1-4939-2987-0_8

Cited by 41 publications

(56 citation statements)

References 19 publications

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“…This technology yields high-dimensional data that provide a systems biology viewpoint of multiple cell types 163 and reveal complex molecular signatures, including signaling networks and functional responses, at the single-cell level. 164,165 Moreover, because data are analyzed in an unsupervised fashion using new computational tools, 166,167 it maximizes the opportunity for discovery of novel cell populations and biomarkers of disease. Similar to transcriptome profiling, mass cytometry promises to prove particularly valuable in interventional models using immunotherapy or experimental infection.…”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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“…Multidimensional cytometry is well suited to this challenge because it can simultaneously characterize known cell types and reveal novel cell subsets (1,2). Mass cytometry uses antibodies to quantify features of individual cells in primary tissues (3,4) and has been applied to characterize cell subsets in human bone marrow, blood, and germinal center tissues as well as diverse murine tissues (5-7). However, mass cytometry remains relatively untested in the context of solid tumors.…”

Section: Introductionmentioning

confidence: 99%

Single Cell Analysis of Human Tissues and Solid Tumors with Mass Cytometry

et al. 2017

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“…As a field, there is a need for standardized procedures and consistent support for sample acquisition as part of clinical trials, especially early phase trials. We recently published detailed step by step mass cytometry focused protocols for human tissue acquisition (58) and unsupervised data analysis (44). Still missing, however, are studies testing the impact of sample acquisition and preparation conditions on a wide number of endpoint assays and standard protocols for data quality assessment that include protocols for data analysis.…”

Section: Conclusion: Toward Clinical Cytomic Monitoringmentioning

confidence: 99%

“…Following processing into single cell suspension, smaller samples of 100,000 to 2 million cells are generally best analyzed immediately, whereas larger samples are typically cryopreserved as aliquots (58). 2) Next, single cells must be detected using a quantitative technique.…”

Section: Figurementioning

confidence: 99%

Systems immune monitoring in cancer therapy

Greenplate

Johnson

Ferrell

et al. 2016

European Journal of Cancer

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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, signaling 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 tumors. This review also discusses the state of the art in single cell tumor 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 tumor 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, signaling 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.

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Characterizing Phenotypes and Signaling Networks of Single Human Cells by Mass Cytometry

Cited by 41 publications

References 19 publications

Pathogenic CD4 + T cells in patients with asthma

Pathogenic CD4 + T cells in patients with asthma

Single Cell Analysis of Human Tissues and Solid Tumors with Mass Cytometry

Systems immune monitoring in cancer therapy

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