Temporal shifts in post-asthmatic immune responses define lung tumor outcomes via strain-specific monocyte reprogramming [ATAC-seq]

ABSTRACT: Epidemiological evidence linking asthma to lung cancer risk remains highly contradictory, presenting asthma as either a risk factor or a protective condition. We hypothesize that this heterogeneity stems from the temporal dynamics of the inflammatory response and the genetic background of the host. Using ovalbumin (OVA)-induced asthma models, we identify a temporal shift in the immune effector cells driving post-asthmatic tumorigenesis. During acute airway inflammation, eosinophil infiltration universally accelerates tumor growth across different mouse strains. However, following the resolution of acute inflammation, tumorigenic outcomes during the recovery phase diverge strictly along genetic lines. The prior asthmatic episode leaves a long-lasting epigenetic imprint on bone marrow myeloid progenitors, establishing an innate immune memory that differentially programs monocytes across strains. In the C57BL/6 background, trained monocytes adopt an oxidative phosphorylation (OXPHOS)-dependent metabolic program, resulting in a functionally suppressive, tissue-remodeling phenotype that directly facilitates lung tumor progression. Conversely, in BALB/c mice, trained monocytes utilize glycolysis to maintain a highly pro-phagocytic state, enabling direct and efficient tumor cell clearance. These findings delineate a strictly innate, biphasic mechanism for post-asthmatic tumorigenesis, demonstrating that patient genetic background and the precise temporal phase of inflammatory disease determine long-term lung cancer susceptibility via divergent monocyte metabolic reprogramming

ORGANISM(S): Mus musculus

PROVIDER: GSE327218 | GEO | 2026/09/23

REPOSITORIES: GEO