PT  - JOURNAL ARTICLE
AU  - Febe van Maldegem
AU  - Karishma Valand
AU  - Megan Cole
AU  - Harshil Patel
AU  - Mihaela Angelova
AU  - Sareena Rana
AU  - Emma Colliver
AU  - Katey Enfield
AU  - Nourdine Bah
AU  - Gavin Kelly
AU  - Victoria Siu Kwan Tsang
AU  - Edurne Mugarza
AU  - Christopher Moore
AU  - Philip Hobson
AU  - Dina Levi
AU  - Miriam Molina-Arcas
AU  - Charles Swanton
AU  - Julian Downward
TI  - Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry
AID  - 10.1101/2021.02.02.429358
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.02.429358
4099  - http://biorxiv.org/content/early/2021/09/21/2021.02.02.429358.short
4100  - http://biorxiv.org/content/early/2021/09/21/2021.02.02.429358.full
AB  - 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.Competing Interest StatementJ.D. has acted as a consultant for AstraZeneca, Bayer, Jubilant, Theras, Vividion and Novartis, and has funded research agreements with BMS, Revolution Medicines and Boehringer Ingelheim. C.S. receives grant support from Archer Dx, AstraZeneca, BoehringerIngelheim and Ono Pharmaceutical; has consulted for AstraZeneca, Bicycle Therapeutics, Celgene, Genentech, GRAIL, GSK, Illumina, Medicxi, MSD, Novartis and the Sarah Cannon Research Institute; receives grant support and has consulted for Bristol Myers Squibb, Pfizer and RocheVentana; is an advisory board member and is involved in trials sponsored by AstraZeneca; has stock options in Apogen Biotechnologies, Epic Sciences, GRAIL; and has stock options and is a cofounder of Achilles Therapeutics. The other authors declare that they have no competing interests.