s41467-021-26214-x (1).pdf (5.35 MB)
Download file

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

Download (5.35 MB)
journal contribution
posted on 13.10.2021, 13:31 by Febe van 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, Julian Downward
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.

Funding

Crick (Grant ID: 10169, Grant title: Swanton FC001169) Crick (Grant ID: 10070, Grant title: Downward FC001070) Crick (Grant ID: 10002, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: 10006, Grant title: STP Flow Cytometry) European Research Council (Grant ID: 834692 - RASImmune, Grant title: ERC 834692 - RASImmune) Wellcome Trust (Grant ID: 103799/A/14/Z, Grant title: WT 103799/A/14/Z) European Commission (Grant ID: 838540 - TRACERxTIME, Grant title: EC 838540 - TRACERxTIME)

History