Abstract 2038: A novel role for the NLRP3 inflammasome in lung cancer

Although significant advances have been made in the diagnosis and treatment of lung cancer, it remains the most fatal cancer worldwide. This poor outcome is mainly due to the limited curative options available especially for advanced cancer stages. About 80% of lung cancers are Non Small Cell Lung Cancers (NSCLC). Although several mutations in oncogenes and tumor genes have been identified in NSCLC, the oncogene K-ras and the Receptor Tyrosine Kinases (RTK) being the most frequently mutated, about 40% of cancers are driven by unidentified mutations. Many cancer cells activate a proinflammatory program to manipulate the host immune system to support their growth. Inflammasomes are crucial effectors of the innate immunity. Upon activation, inflammasomes assemble into multiprotein complexes controlling the activation of the inflammatory caspase-1 and the maturation of the pro-Interleukin-1beta (pro-IL-1b) and the pro-IL-18 into active cytokines. The NLRP3 inflammasome detects pathogens, airborne pollutants but also self-danger signals released by dying cells. In the lung, hyperactivation of this complex upon bleomycin or asbestos exposure drives an inflammatory response resulting in lung fibrosis. Published large-scale genomic analyses of NSCLC identified somatic mutations in the NLRP3 gene and scored NLRP3 as a putative oncogene. Little is known about the role of the NLRP3 inflammasome in lung cancer. We speculated that the NLRP3 inflammasome could play a prominent role in NSCLC and studied the function of NLRP3 inflammasome in human non-transformed and transformed lung epithelial cells. Our data unravel new functions for the NLRP3 inflammasome in DNA damage sensing and unexpectedly suggest that NLRP3 could act as a tumor suppressor gene in lung cancer. Citation Format: Virginie Petrilli, Melanie Bodnar, Baptiste Guey, Sabine Hacot, Sylvie Lantuejoul. A novel role for the NLRP3 inflammasome in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2038. doi:10.1158/1538-7445.AM2015-2038