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Nat Commun ; 12(1): 5906, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625563

RESUMO

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.


Assuntos
Citometria por Imagem/métodos , Oncogenes , Microambiente Tumoral/imunologia , Animais , Anticorpos , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/imunologia , Modelos Animais de Doenças , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Oncogenes/efeitos dos fármacos , Linfócitos T , Microambiente Tumoral/efeitos dos fármacos
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