AUTHOR=Farahmand Pooyeh , Gyuraszova Katarina , Rooney Claire , Raffo-Iraolagoitia Ximena L. , Jayasekera Geeshath , Hedley Ann , Johnson Emma , Chernova Tatyana , Malviya Gaurav , Hall Holly , Monteverde Tiziana , Blyth Kevin , Duffin Rodger , Carlin Leo M. , Lewis David , Le Quesne John , MacFarlane Marion , Murphy Daniel J. 

TITLE=Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma

JOURNAL=Frontiers in Toxicology

VOLUME=5

YEAR=2023

URL=https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2023.1200650

DOI=10.3389/ftox.2023.1200650

ISSN=2673-3080

ABSTRACT=<p><bold>Hypothesis:</bold> Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> 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.</p>