Abstract 196: Lung inflammation accelerates tumor progression in a mouse model of oncogenic KRAS driven lung adenocarcinoma.

Abstract Recent studies of human tissue samples in various organs including the lung have revealed the presence of canonical oncogenic mutations at rates higher than known incidence rates of cancers associated with these tissues. Other work has linked diverse inflammatory diseases to increased incidence rates of cancers associated with the involved organs. In the context of lung adenocarcinoma (LUAD), inflammatory lung diseases may produce a favorable environment for the outgrowth of tumors, and characterizing how this may occur could uncover avenues for LUAD prevention. Using a transgenic mouse model where LUAD is initiated by inducing expression of oncogenic KRAS and the fluorophore tdTomato in normal alveolar type II cells via delivery of Cre-expressing virus into the lung, we demonstrated that a range of inflammatory insults accelerated early tumor growth. Modelling of idiopathic pulmonary fibrosis and bacterial or viral lung infections in these tumor bearing mice each resulted in an increase in average tumor size and total tumor burden at both early and late timepoints of tumor progression, despite showing many divergent impacts on lung immune populations and signaling factors as characterized through flow cytometry, RNA sequencing, and ELISAs. Immunofluorescence staining of early lesions allowed us to quantify the increase in lesion size under inflammatory conditions and to investigate the association of immune cells with these small lesions, revealing that KI-67+ F4/80+ macrophages showed increased density proximal to lesions under all inflammatory conditions. We are actively working to uncover the points of communication between immune populations and early cancer cells that result in this accelerated tumor growth under these conditions. We have observed that in our LUAD mouse model tumor growth is accelerated by exposure to lung inflammation, and through characterization of the inflamed immune microenvironment and communication between immune and cancer cells during inflammation that mediate accelerated growth, this project aims to identify molecular targets for LUAD prevention. Citation Format: Samantha A. Nelson, Jacob Kassama, Christina M. Cabana, Alexandria M. Jefferson, Tyler E. Jacks. Lung inflammation accelerates tumor progression in a mouse model of oncogenic KRAS driven lung adenocarcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 196.