Congratulations to Pooyeh Farahmand of the Murphy lab in Glasgow and collaborators (full authors list below) on publication of their paper ‘Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma‘ in Frontiers in Toxicology

Abstract

Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations.

Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration.

Results: Injection of asbestos dramatically accelerated disease onset and end-stage tumour burden. Tumours developed in the presence of asbestos showed increased macrophage infiltration. Pharmacological suppression of macrophages in mice with established tumours failed to extend survival or to enhance response to chemotherapy.

Conclusion: Asbestos-driven inflammation contributes to the severity of mesothelioma beyond the acquisition of rate-limiting mutations, however, targeted suppression of macrophages in established epithelioid mesothelioma showed no therapeutic benefit.

Authors:

Pooyeh Farahmand¹, Katarina Gyuraszova¹, Claire Rooney^1,2, Ximena L. Raffo-Iraolagoitia³, Geeshath Jayasekera⁴, Ann Hedley³, Emma Johnson³, Tatyana Chernova⁵, Gaurav Malviya³, Holly Hall³, Tiziana Monteverde¹, Kevin Blyth^1,3,4, Rodger Duffin⁶, Leo M. Carlin^1,3, David Lewis^1,3, John Le Quesne^1,3,7, Marion MacFarlane⁵*^† and Daniel J. Murphy^1,3*^†

¹School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom
²Department of Respiratory Medicine, Royal Infirmary, Glasgow, United Kingdom
³CRUK Beatson Institute, Garscube Estate, Glasgow, United Kingdom
⁴Glasgow Pleural Disease Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom
⁵MRC Toxicology Unit, University of Cambridge, Cambridge, United Kingdom
⁶Centre for Inflammation Research, Edinburgh, United Kingdom
⁷Department of Histopathology, Queen Elizabeth University Hospital, Glasgow, United Kingdom
*Correspondence: Daniel J. Murphy, Daniel.murphy@glasgow.ac.uk; Marion MacFarlane, Mm2312@mrc-tox.cam.ac.uk
^†These authors share senior authorship