Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry
Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry
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.
Rana Sareena、Enfield Katey、van Maldegem Febe、Patel Harshil、Bah Nourdine、Hobson Philip、Swanton Charles、Colliver Emma、Molina-Arcas Miriam、Kelly Gavin、Valand Karishma、Moore Christopher、Mugarza Edurne、Downward Julian、Cole Megan、Levi Dina、Tsang Victoria Siu Kwan、Angelova Mihaela
Oncogene Biology Laboratory, The Francis Crick Institute||Lung Cancer Group, Division of Molecular Pathology, Institute of Cancer ResearchCancer Evolution and Genome Instability Laboratory, The Francis Crick InstituteOncogene Biology Laboratory, The Francis Crick Institute||Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Location VUMCBioinformatics and Biostatistics Science Technology Platform, The Francis Crick InstituteBioinformatics and Biostatistics Science Technology Platform, The Francis Crick InstituteFlow Cytometry Science Technology Platform, The Francis Crick InstituteCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute||Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer InstituteCancer Evolution and Genome Instability Laboratory, The Francis Crick InstituteOncogene Biology Laboratory, The Francis Crick InstituteBioinformatics and Biostatistics Science Technology Platform, The Francis Crick InstituteOncogene Biology Laboratory, The Francis Crick InstituteOncogene Biology Laboratory, The Francis Crick InstituteOncogene Biology Laboratory, The Francis Crick InstituteOncogene Biology Laboratory, The Francis Crick Institute||Lung Cancer Group, Division of Molecular Pathology, Institute of Cancer ResearchOncogene Biology Laboratory, The Francis Crick InstituteFlow Cytometry Science Technology Platform, The Francis Crick InstituteOncogene Biology Laboratory, The Francis Crick InstituteCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute
医学研究方法肿瘤学基础医学
Rana Sareena,Enfield Katey,van Maldegem Febe,Patel Harshil,Bah Nourdine,Hobson Philip,Swanton Charles,Colliver Emma,Molina-Arcas Miriam,Kelly Gavin,Valand Karishma,Moore Christopher,Mugarza Edurne,Downward Julian,Cole Megan,Levi Dina,Tsang Victoria Siu Kwan,Angelova Mihaela.Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry[EB/OL].(2025-03-28)[2025-06-12].https://www.biorxiv.org/content/10.1101/2021.02.02.429358.点此复制
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