Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry.
Animals
Antibodies
Antineoplastic Agents
/ pharmacology
Carcinoma, Non-Small-Cell Lung
/ diagnostic imaging
Disease Models, Animal
Image Cytometry
/ methods
Lung Neoplasms
/ diagnostic imaging
Macrophages
Mice
Mice, Inbred C57BL
Oncogenes
/ drug effects
T-Lymphocytes
Tumor Microenvironment
/ drug effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 10 2021
08 10 2021
Historique:
received:
05
03
2021
accepted:
20
09
2021
entrez:
9
10
2021
pubmed:
10
10
2021
medline:
3
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34625563
doi: 10.1038/s41467-021-26214-x
pii: 10.1038/s41467-021-26214-x
pmc: PMC8501076
doi:
Substances chimiques
Antibodies
0
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5906Subventions
Organisme : Wellcome Trust
ID : FC001070
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 103799/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001070
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C33499/A20265
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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