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Use of Imaging Mass Cytometry in Studies of the Tissue Microenvironment

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Biomarkers of the Tumor Microenvironment

Abstract

Techniques for analysis of tissues, such as immunofluorescence, immunohistochemistry and flow cytometry-based approaches for analysis of cell suspensions, have allowed the characterization of single cells within heterogeneous cell populations. However, the limitations in the number of parameters that can be simultaneously assessed have hampered advances in understanding complex tissue systems. The advent of single-cell mass cytometry, cytometry by time of flight (CyTOF), which uses metal-tagged antibodies, has made it possible to overcome these constraints as CyTOF allows the detection of a large number of cell markers in parallel. A more recently developed technique, imaging mass cytometry (IMC), has pushed the boundaries even further. By combining the transformational power of mass spectrometry with tissue-based approaches, the IMC allows for high-dimensional analysis of tissues with spatial resolution. However, different challenges must be faced to fully exploit the capabilities of IMC. Here, we provide an overview of IMC, covering the basic principles of the technology, the types of tissues used, marker selection, and antibody panel design. This technical discussion is followed by specific examples of applications of IMC to breast cancer tissues, paediatric brain tumours, and paraneoplastic cerebellar degeneration with a focus on our own research. Computational tools used to analyze the resulting multi-parametric data are also addressed.

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Notes

  1. 1.

    MMTV-PyMT = mouse mammary tumour virus-polyoma middle tumour-antigen.

  2. 2.

    METABRIC cohort = Molecular Taxonomy of Breast Cancer International Consortium; ten subtypes or integrative clusters of breast cancer identified through an integrated analysis of genomic and transcriptomic data.

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Acknowledgements

MV is a Children with Cancer UK Fellow (grant 16-234) and acknowledges Children with Cancer UK and The Cure Starts Now, Fondazione Heal and Banca D´Italia for supporting this study. LLP acknowledges Fondazione AIRC. MV and LLP are grateful to Dr. Angela Mastronuzzi (Head of Neuro-Oncology Unit, OPBG), Dr. Andrea Carai (Oncological Neurosurgery Unit, OPBG), and Dr. Sabrina Rossi (Pathology Lab, OPBG) for clinical and pathological assessment of the DIPG case and the patient family. DB and FQ are funded by a CRUK ‘Grand Challenge’ grant (A24042), DB acknowledges the entire IMAXT project team and in particular the staff of the University of Cambridge Institute of Astronomy for the work performed on IMC data analysis and Dr. Bernd Bodenmiller and his laboratory, at the University of Zurich, for the many discussions and suggestions in implementing mass cytometry.

SG and IH would like to thank senior research technician, Bendik Nordanger, at the Department of Clinical Medicine, University of Bergen for his support in preparing PCD post-mortem TMA, and Head Engineer at the Core Facility for Flow Cytometry, Jørn Skavland, Department of Clinical Science, University of Bergen, for his technical support. Research grants from Torbjørg Hauges legacy supported this study. SG and IH are funded by NeuroSys-Med and Helse Vest.

Author information

Author notes

  1. Ida Herdlevær, Lucia Lisa Petrilli, Fatime Qosaj, Maria Vinci, Dario Bressan and Sonia Gavasso contributed equally with all other contributors.

Authors and Affiliations

  1. Department of Neurology, Haukeland University Hospital, Bergen, Norway

    Ida Herdlevær & Sonia Gavasso

  2. Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Ida Herdlevær & Sonia Gavasso

  3. Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway

    Ida Herdlevær & Sonia Gavasso

  4. Department of Onco-Haematology, Gene and Cell Therapy, Bambino Gesù Children’s Hospital-IRCCS, Rome, Italy

    Lucia Lisa Petrilli & Maria Vinci

  5. CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK

    Fatime Qosaj & Dario Bressan

Authors
  1. Ida Herdlevær
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  2. Lucia Lisa Petrilli
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  3. Fatime Qosaj
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  4. Maria Vinci
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  5. Dario Bressan
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  6. Sonia Gavasso
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Corresponding author

Correspondence to Sonia Gavasso .

Editor information

Editors and Affiliations

  1. Centre for Cancer Biomarkers CCBIO Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Lars A. Akslen

  2. Department of Surgery, Harvard Medical School, Vascular Biology Program, Boston Children’s Hospital, Boston, USA

    Randolph S. Watnick

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Herdlevær, I., Petrilli, L.L., Qosaj, F., Vinci, M., Bressan, D., Gavasso, S. (2022). Use of Imaging Mass Cytometry in Studies of the Tissue Microenvironment. In: Akslen, L.A., Watnick, R.S. (eds) Biomarkers of the Tumor Microenvironment. Springer, Cham. https://doi.org/10.1007/978-3-030-98950-7_20

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  • DOI: https://doi.org/10.1007/978-3-030-98950-7_20

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-98949-1

  • Online ISBN: 978-3-030-98950-7

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