Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry.
Date
2021-10-08ICR Author
Author
van Maldegem, F
Valand, K
Cole, M
Patel, H
Angelova, M
Rana, S
Colliver, E
Enfield, K
Bah, N
Kelly, G
Tsang, VSK
Mugarza, E
Moore, C
Hobson, P
Levi, D
Molina-Arcas, M
Swanton, C
Downward, J
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Animals
Antibodies
Antineoplastic Agents
Carcinoma, Non-Small-Cell Lung
Disease Models, Animal
Image Cytometry
Lung Neoplasms
Macrophages
Mice
Mice, Inbred C57BL
Oncogenes
T-Lymphocytes
Tumor Microenvironment
Research team
Lung Cancer Group
Language
eng
Date accepted
2021-09-20
License start date
2021-10-08
Citation
Nature Communications, 2021, 12 (1), pp. 5906 -
Publisher
NATURE PORTFOLIO