The road ahead: Implementing mass cytometry in clinical studies, one cell at a time

Baca, Quentin; Cosma, Antonio; Nolan, Garry P.; Gaudillière, Brice

doi:10.1002/cyto.b.21497

Cited by 21 publications

(19 citation statements)

References 20 publications

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“…The general concept of utilizing mass cytometry to characterize immune states associated with disease progression or response to therapy has been demonstrated in multiple clinical contexts , including malignancies , rheumatological diseases , aging , traumatic injury , and pregnancy . While the use of mass cytometry in sepsis is still in its infancy , observational studies in the context of traumatic injury provide the groundwork for the deep immune profiling of complex inflammatory states such as sepsis.…”

Section: The Promise Of Cytometry By Time Of Flight Mass Spectrometrymentioning

confidence: 99%

How Clinical Flow Cytometry Rebooted Sepsis Immunology

et al. 2019

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On May 2017, the World Health Organization (WHO) recognized sepsis as a global health priority by adopting a resolution to improve the prevention, diagnosis, and management of this deadly disease. While it has long been known that sepsis deeply perturbs immune homeostasis by inducing a tremendous systemic inflammatory response, pivotal observations based on clinical flow cytometry indicate that sepsis indeed initiates a more complex immune response that varies over time, with the concomitant occurrence of both pro-and anti-inflammatory mechanisms. As a resultant, some septic patients enter a stage of protracted immunosuppression. This paved the way for immunostimulation approaches in sepsis. Clinical flow cytometry permitted this evolution by drawing a new picture of pathophysiology and reshaping immune trajectories in patients. Additional information from cytometry by time of flight mass cytometry and other highdimensional flow cytometry platform should rapidly enrich our understanding of this complex disease. This review reports on landmarks of clinical flow cytometry in sepsis and how this single-cell analysis technique permitted to breach the wall of decades of unfruitful anti-inflammatory-based clinical trials in sepsis.On May 2017, the World Health Organization (WHO) recognized sepsis as a global health priority by adopting a resolution to improve the prevention, diagnosis, and management of this deadly disease (1). Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection (2). Septic shock is the most severe form of sepsis in which hypotension persists despite adequate volume resuscitation thus requiring the use of vasopressors. According to recent definitions, in response to an infectious trigger, the unbalanced host (immune) response is at the center of sepsis pathophysiology (2).Sepsis represents a major healthcare problem worldwide. As an example, in the US, sepsis is more frequent than myocardial infarction, breast, or colon cancers (3-6). Recent modeling of available data determined the number of cases of sepsis in the entire world to over 20-25 million corresponding to >6 million deaths per annum (7,8). Over the years, 28-day mortality has remained high, ranging from 20% for sepsis to over 40% for septic shock despite improvement in patients' care (fluid resuscitation, source control, antimicrobial therapy). Whereas few therapeutic options evaluated in phase II clinical trials have demonstrated the potential efficacy of immunostimulation in sepsis, to date, no therapeutic intervention targeting host response has specifically been approved and sepsis remains the leading cause of mortality in intensive care units (ICU)(9,10). In addition, sepsis incidence has dramatically increased over the past decade and is expected to further augment. This rising

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Section: The Promise Of Cytometry By Time Of Flight Mass Spectrometrymentioning

confidence: 99%

How Clinical Flow Cytometry Rebooted Sepsis Immunology

et al. 2019

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“…Pharmacodynamic analysis of TKI effect on Bcr-Abl1 tyrosine kinase activity and subsequent downstream signal transduction in CML patients has been technically challenging and thus rarely exploited in clinical trials. 14 , 15 However, recent advances in single cell analysis of intracellular signal transduction show promise both in diagnostics and in therapeutic leukemia monitoring. 16 – 18 Cytometry by Time of Flight (CyTOF) allows single cell characterization of immunophenotypes and intracellular signaling status in healthy individuals 19 , 20 and patients with hematologic malignancies.…”

Section: Introductionmentioning

confidence: 99%

Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib

et al. 2017

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Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1IS at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. (clinicaltrials.gov identifier: 01061177)

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“…Mass cytometry has been adopted by many clinical and translational labs worldwide to monitor changes of the immune system and other heterogeneous cellular entities in great detail and at single‐cell resolution . However, certain projects require handling of many samples from large patient cohorts, on‐demand processing of fresh cells, or longitudinal sampling and data acquisition.…”

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Stabilizing Antibody Cocktails for Mass Cytometry

et al. 2019

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Mass cytometry is increasingly employed in larger immune profiling studies involving data acquisitions across several days and multiple sites. For gaining a maximum of information from respective data by computational analyses, several techniques have been developed to minimize noise in mass cytometric data sets, such as sample banking, standardized instrument setup, sample barcoding, and signal normalization. However, the repeated preparation of cocktails composed of isotope-tagged antibodies remained a significant source of error. We here show that premixed antibody cocktails fail to deliver expected staining patterns when stored at 4 C for 4 weeks. As a solution, we developed and tested a cryopreservation method for highly multiplexed antibody cocktails for mass cytometry including lanthanide, palladium, and platinum conjugates that yielded stable staining patterns for at least 9 months when stored at temperatures below −80 C. Using frozen aliquots of antibody cocktails is an economic and flexible approach to significantly improve data consistency in large mass cytometry studies with repetitive staining/measurement cycles spanning several days or involving multiple data acquisition sites.

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The road ahead: Implementing mass cytometry in clinical studies, one cell at a time

Cited by 21 publications

References 20 publications

How Clinical Flow Cytometry Rebooted Sepsis Immunology

How Clinical Flow Cytometry Rebooted Sepsis Immunology

Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib

Stabilizing Antibody Cocktails for Mass Cytometry

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