Role of the Inflammasome in Asbestos-Induced Mesothelioma Formation

: The investigations proposed in this idea award grant are aimed at addressing the requirement of asbestos-induced inflammation in the pathogenesis of malignant mesothelioma (MM). Cancer-related inflammation (CRI) within the tumor microenvironment contributes to tumor progression in many human malignancies. MM tumor samples have hallmarks of CRI including macrophage infiltration and inflammatory cytokine production. We intend to evaluate the role of asbestos-induced inflammation in the formation of MM by genetically and pharmacologically inhibiting inflammasome-mediated inflammation in mouse models of MM and determine whether this physiological response is required for tumor development. The overarching goal is to provide the first in vivoevidence of whether inflammation directly contributes to the development of asbestos-induced MM. The proposed investigations may also implicate inflammasome-mediated CRI as a potential target for the prevention or treatment of MM.