Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry

Febe Maldegem (), Karishma Valand, Megan Cole, Harshil Patel, Mihaela Angelova, Sareena Rana, Emma Colliver, Katey Enfield, Nourdine Bah, Gavin Kelly, Victoria Siu Kwan Tsang, Edurne Mugarza, Christopher Moore, Philip Hobson, Dina Levi, Miriam Molina-Arcas, Charles Swanton and Julian Downward ()
Additional contact information
Febe Maldegem: Oncogene Biology Laboratory, The Francis Crick Institute
Karishma Valand: Oncogene Biology Laboratory, The Francis Crick Institute
Megan Cole: Oncogene Biology Laboratory, The Francis Crick Institute
Harshil Patel: Bioinformatics and Biostatistics Science Technology Platform, The Francis Crick Institute
Mihaela Angelova: Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute
Sareena Rana: Oncogene Biology Laboratory, The Francis Crick Institute
Emma Colliver: Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute
Katey Enfield: Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute
Nourdine Bah: Bioinformatics and Biostatistics Science Technology Platform, The Francis Crick Institute
Gavin Kelly: Bioinformatics and Biostatistics Science Technology Platform, The Francis Crick Institute
Victoria Siu Kwan Tsang: Oncogene Biology Laboratory, The Francis Crick Institute
Edurne Mugarza: Oncogene Biology Laboratory, The Francis Crick Institute
Christopher Moore: Oncogene Biology Laboratory, The Francis Crick Institute
Philip Hobson: Flow Cytometry Science Technology Platform, The Francis Crick Institute
Dina Levi: Flow Cytometry Science Technology Platform, The Francis Crick Institute
Miriam Molina-Arcas: Oncogene Biology Laboratory, The Francis Crick Institute
Charles Swanton: Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute
Julian Downward: Oncogene Biology Laboratory, The Francis Crick Institute

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Mouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy. Here we present a workflow for studying the TME using imaging mass cytometry with a panel of 27 antibodies on frozen mouse tissues. We optimise and validate image segmentation strategies and automate the process in a Nextflow-based pipeline (imcyto) that is scalable and portable, allowing for parallelised segmentation of large multi-image datasets. With these methods we interrogate the remodelling of the TME induced by a KRAS G12C inhibitor in an immune competent mouse orthotopic lung cancer model, highlighting the infiltration and activation of antigen presenting cells and effector cells.

Date: 2021
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DOI: 10.1038/s41467-021-26214-x

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